Search

Your search keyword '"Yves d'Aubenton-Carafa"' showing total 72 results
Start Over Author "Yves d'Aubenton-Carafa"
72 results on '"Yves d'Aubenton-Carafa"'

1. Systematic comparison of small RNA library preparation protocols for next-generation sequencing

Author

Cloelia Dard-Dascot, Delphine Naquin, Yves d’Aubenton-Carafa, Karine Alix, Claude Thermes, and Erwin van Dijk

Subjects
Small RNA, Bias, Library preparation, Next-generation sequencing, NGS, 2’-O-methyl RNA, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Next-generation sequencing technologies have revolutionized the study of small RNAs (sRNAs) on a genome-wide scale. However, classical sRNA library preparation methods introduce serious bias, mainly during adapter ligation steps. Several types of sRNA including plant microRNAs (miRNA), piwi-interacting RNAs (piRNA) in insects, nematodes and mammals, and small interfering RNAs (siRNA) in insects and plants contain a 2’-O-methyl (2’-OMe) modification at their 3′ terminal nucleotide. This inhibits 3′ adapter ligation and makes library preparation particularly challenging. To reduce bias, the NEBNext kit (New England Biolabs) uses polyethylene glycol (PEG), the NEXTflex V2 kit (BIOO Scientific) uses both randomised adapters and PEG, and the novel SMARTer (Clontech) and CATS (Diagenode) kits avoid ligation altogether. Here we compared these methods with Illumina’s classical TruSeq protocol regarding the detection of normal and 2’ OMe RNAs. In addition, we modified the TruSeq and NEXTflex protocols to identify conditions that improve performance. Results Among the five kits tested with their respective standard protocols, the SMARTer and CATS kits had the lowest levels of bias but also had a strong formation of side products, and as a result performed relatively poorly with biological samples; NEXTflex detected the largest numbers of different miRNAs. The use of a novel type of randomised adapters called MidRand-Like (MRL) adapters and PEG improved the detection of 2’ OMe RNAs both in the TruSeq as well as in the NEXTflex protocol. Conclusions While it is commonly accepted that biases in sRNA library preparation protocols are mainly due to adapter ligation steps, the ligation-free protocols were not the best performing methods. Our modified versions of the TruSeq and NEXTflex protocols provide an improved tool for the study of 2’ OMe RNAs.

Published
2018
Full Text
View/download PDF

2. Replication landscape of the human genome

Author

Nataliya Petryk, Malik Kahli, Yves d'Aubenton-Carafa, Yan Jaszczyszyn, Yimin Shen, Maud Silvain, Claude Thermes, Chun-Long Chen, and Olivier Hyrien

Subjects
Science
Abstract

The physical origin and termination sites of DNA replication in human cells have remained elusive. Here the authors use Okazaki fragment sequencing to reveal global replication patterns and show how chromatin and transcription modulate the process.

Published
2016
Full Text
View/download PDF

3. Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines.

Author

Antoine Baker, Benjamin Audit, Chun-Long Chen, Benoit Moindrot, Antoine Leleu, Guillaume Guilbaud, Aurélien Rappailles, Cédric Vaillant, Arach Goldar, Fabien Mongelard, Yves d'Aubenton-Carafa, Olivier Hyrien, Claude Thermes, and Alain Arneodo

Subjects
Biology (General), QH301-705.5
Abstract

In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome.

Published
2012
Full Text
View/download PDF

4. Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome.

Author

Guillaume Guilbaud, Aurélien Rappailles, Antoine Baker, Chun-Long Chen, Alain Arneodo, Arach Goldar, Yves d'Aubenton-Carafa, Claude Thermes, Benjamin Audit, and Olivier Hyrien

Subjects
Biology (General), QH301-705.5
Abstract

Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general model for their replication kinetics.

Published
2011
Full Text
View/download PDF

5. Neurodevelopment genes in lampreys reveal trends for forebrain evolution in craniates.

Author

Adèle Guérin, Yves d'Aubenton-Carafa, Emna Marrakchi, Corinne Da Silva, Patrick Wincker, Sylvie Mazan, and Sylvie Rétaux

Subjects
Medicine, Science
Abstract

The forebrain is the brain region which has undergone the most dramatic changes through vertebrate evolution. Analyses conducted in lampreys are essential to gain insight into the broad ancestral characteristics of the forebrain at the dawn of vertebrates, and to understand the molecular basis for the diversifications that have taken place in cyclostomes and gnathostomes following their splitting. Here, we report the embryonic expression patterns of 43 lamprey genes, coding for transcription factors or signaling molecules known to be involved in cell proliferation, stemcellness, neurogenesis, patterning and regionalization in the developing forebrain. Systematic expression patterns comparisons with model organisms highlight conservations likely to reflect shared features present in the vertebrate ancestors. They also point to changes in signaling systems -pathways which control the growth and patterning of the neuroepithelium-, which may have been crucial in the evolution of forebrain anatomy at the origin of vertebrates.

Published
2009
Full Text
View/download PDF

7. OKseqHMM: a genome-wide replication fork directionality analysis toolkit

Author

Yaqun Liu, Xia Wu, Yves D’aubenton-Carafa, Claude Thermes, Chun-Long Chen, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), YPI program of I. Curie, ATIP-Avenir program from Centre national de la recherche scientifique (CNRS) and Plan Cancer [ATIP/AVENIR: N◦18CT014-00], Institut National du Cancer (INCa) [PLBIO19-076], ANR-19-CE12-0016,ReDeFINe,Hybrides ARN:ADN et instabilité des fourches de réplication(2019), and ANR-19-CE12-0020,TELOCHROM,Mécanismes de réplication de l'hétérochromatine: lien avec les télomères(2019)

Subjects
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Abstract

MotivationDuring each cell division, tens of thousands of DNA replication origins are coordinately activated to ensure the complete duplication of the entire human genome. However, the progression of replication forks can be challenged by numerous factors. One such factor is transcription-replication conflicts (TRC), which can either be co-directional or head-on with the latter being revealed as more dangerous for genome integrity.ResultsIn order to study the direction of replication fork movement and TRC, we developed a bioinformatics tool, called OKseqHMM, to directly measure the genome-wide replication fork directionality (RFD) as well as replication initiation and termination from data obtained by Okazaki fragment sequencing (OK-Seq) and related techniques.Availability and ImplementationWe have gathered and analyzed OK-seq data from a large number of organisms including yeast, mouse and human, to generate high-quality RFD profiles and determine initiation zones and termination zones by using Hidden Markov Model (HMM) algorithm (all tools and data are available at https://github.com/CL-CHEN-Lab/OK-Seq). In addition, we have extended our analysis to data obtained by related techniques, such as eSPAN and TrAEL-seq, which also contain RFD information. Our works, therefore, provide an important tool and resource for the community to further study TRC and genome instability, in a wide range of cell line models and growth conditions, which is of prime importance for human health.ContactChun-Long Chen (Institut Curie), chunlong.chen@curie.frCategoryGenome analysis

Published
2022
Full Text
View/download PDF

13. In vivoSELEX reveals novel sequence and structural determinants of Nrd1-Nab3-Sen1-dependent transcription termination

Author

Richard Štefl, Jocelyne Boulay, Karel Kubíček, Yves D'Aubenton‐Carafa, Rajani Kanth Gudipati, Domenico Libri, Fruzsina Hobor, and Odil Porrua

Subjects
Genetics, General Immunology and Microbiology, RNA recognition motif, General Neuroscience, Termination factor, RNA, RNA-binding protein, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Terminator (genetics), Transcription (biology), Small nucleolar RNA, Molecular Biology, Systematic evolution of ligands by exponential enrichment
Abstract

The Nrd1-Nab3-Sen1 (NNS) complex pathway is responsible for transcription termination of cryptic unstable transcripts and sn/snoRNAs. The NNS complex recognizes short motifs on the nascent RNA, but the presence of these sequences alone is not sufficient to define a functional terminator. We generated a homogeneous set of several hundreds of artificial, NNS-dependent terminators with an in vivo selection approach. Analysis of these terminators revealed novel and extended sequence determinants for transcription termination and NNS complex binding as well as supermotifs that are critical for termination. Biochemical and structural data revealed that affinity and specificity of RNA recognition by Nab3p relies on induced fit recognition implicating an α-helical extension of the RNA recognition motif. Interestingly, the same motifs can be recognized by the NNS or the mRNA termination complex depending on their position relative to the start of transcription, suggesting that they function as general transcriptional insulators to prevent interference between the non-coding and the coding yeast transcriptomes.

Published
2012
Full Text
View/download PDF

14. Widespread bidirectional promoters are the major source of cryptic transcripts in yeast

Author

Lars M. Steinmetz, Zhenyu Xu, Christophe Malabat, Yves d'Aubenton-Carafa, Helen Neil, and Alain Jacquier

Subjects
Genetics, Regulation of gene expression, Multidisciplinary, biology, Fungal genetics, RNA polymerase II, Promoter, medicine.disease, Transcription (biology), medicine, biology.protein, Serial analysis of gene expression, Gene, Transcriptional noise
Abstract

Pervasive and hidden transcription is widespread in eukaryotes, but its global level, the mechanisms from which it originates and its functional significance are unclear. Cryptic unstable transcripts (CUTs) were recently described as a principal class of RNA polymerase II transcripts in Saccharomyces cerevisiae. These transcripts are targeted for degradation immediately after synthesis by the action of the Nrd1-exosome-TRAMP complexes. Although CUT degradation mechanisms have been analysed in detail, the genome-wide distribution at the nucleotide resolution and the prevalence of CUTs are unknown. Here we report the first high-resolution genomic map of CUTs in yeast, revealing a class of potentially functional CUTs and the intrinsic bidirectional nature of eukaryotic promoters. An RNA fraction highly enriched in CUTs was analysed by a 3' Long-SAGE (serial analysis of gene expression) approach adapted to deep sequencing. The resulting detailed genomic map of CUTs revealed that they derive from extremely widespread and very well defined transcription units and do not result from unspecific transcriptional noise. Moreover, the transcription of CUTs predominantly arises within nucleosome-free regions, most of which correspond to promoter regions of bona fide genes. Some of the CUTs start upstream from messenger RNAs and overlap their 5' end. Our study of glycolysis genes, as well as recent results from the literature, indicate that such concurrent transcription is potentially associated with regulatory mechanisms. Our data reveal numerous new CUTs with such a potential regulatory role. However, most of the identified CUTs corresponded to transcripts divergent from the promoter regions of genes, indicating that they represent by-products of divergent transcription occurring at many and possibly most promoters. Eukaryotic promoter regions are thus intrinsically bidirectional, a fundamental property that escaped previous analyses because in most cases divergent transcription generates short-lived unstable transcripts present at very low steady-state levels.

Published
2009
Full Text
View/download PDF

16. Replication landscape of the human genome

Author

Maud Silvain, Olivier Hyrien, Claude Thermes, Chun-Long Chen, Yimin Shen, Yan Jaszczyszyn, Malik Kahli, Nataliya Petryk, Yves d'Aubenton-Carafa, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GRECH, Cécile, Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie de l'ENS Paris (UMR 8197/1024) ( IBENS ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS)

Subjects
0301 basic medicine, DNA Replication, Transcription, Genetic, Science, [SDV]Life Sciences [q-bio], Origin Recognition Complex, General Physics and Astronomy, Replication Origin, Biology, Origin of replication, Pre-replication complex, General Biochemistry, Genetics and Molecular Biology, Article, Histones, 03 medical and health sciences, Humans, Enhancer, Genetics, Multidisciplinary, Binding Sites, Okazaki fragments, [ SDV ] Life Sciences [q-bio], Genome, Human, DNA replication, General Chemistry, DNA, Sequence Analysis, DNA, Chromatin, [SDV] Life Sciences [q-bio], 030104 developmental biology, Licensing factor, Evolutionary biology, Origin recognition complex
Abstract

Despite intense investigation, human replication origins and termini remain elusive. Existing data have shown strong discrepancies. Here we sequenced highly purified Okazaki fragments from two cell types and, for the first time, quantitated replication fork directionality and delineated initiation and termination zones genome-wide. Replication initiates stochastically, primarily within non-transcribed, broad (up to 150 kb) zones that often abut transcribed genes, and terminates dispersively between them. Replication fork progression is significantly co-oriented with the transcription. Initiation and termination zones are frequently contiguous, sometimes separated by regions of unidirectional replication. Initiation zones are enriched in open chromatin and enhancer marks, even when not flanked by genes, and often border ‘topologically associating domains' (TADs). Initiation zones are enriched in origin recognition complex (ORC)-binding sites and better align to origins previously mapped using bubble-trap than λ-exonuclease. This novel panorama of replication reveals how chromatin and transcription modulate the initiation process to create cell-type-specific replication programs., The physical origin and termination sites of DNA replication in human cells have remained elusive. Here the authors use Okazaki fragment sequencing to reveal global replication patterns and show how chromatin and transcription modulate the process.

Published
2016
Full Text
View/download PDF

17. Systematic comparison of small RNA library preparation protocols for next-generation sequencing

Author

Cloelia Dard-Dascot, Delphine Naquin, Yves d’Aubenton-Carafa, Karine Alix, Erwin van Dijk, Claude Thermes, Plateforme de séquençage à haut débit (NGS), Département Plateforme (PF I2BC), Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Van Dijk, Erwin, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-AgroParisTech-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Recherche Agronomique (INRA), ProdInra, Archive Ouverte, Institut de Biologie Intégrative de la Cellule, Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), National Center for Scientific Research (CNRS), French Alternative Energies and Atomic Energy Commission (CEA), Paris-Sud University, Plateforme de séquençage à haut débit ( NGS ), Département Plateforme ( PF I2BC ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) ( GQE-Le Moulon ), and Institut National de la Recherche Agronomique ( INRA ) -Université Paris-Sud - Paris 11 ( UP11 ) -AgroParisTech-Centre National de la Recherche Scientifique ( CNRS )

Subjects
0301 basic medicine, Small RNA, Library preparation, lcsh:QH426-470, lcsh:Biotechnology, [SDV]Life Sciences [q-bio], Piwi-interacting RNA, Computational biology, Biology, DNA sequencing, 03 medical and health sciences, 0302 clinical medicine, Adapter (genetics), New england, Bias, lcsh:TP248.13-248.65, microRNA, Genetics, Animals, Humans, small RNA, Gene Library, [ SDV ] Life Sciences [q-bio], Sequence Analysis, RNA, Methodology Article, Computational Biology, High-Throughput Nucleotide Sequencing, Reproducibility of Results, Plants, [SDV] Life Sciences [q-bio], MicroRNAs, lcsh:Genetics, 030104 developmental biology, Next-generation sequencing, NGS, 2 '-O-methyl RNA, BIAS, 030220 oncology & carcinogenesis, Nucleic Acid Conformation, 2’-O-methyl RNA, next-generation sequencing, DNA microarray, Biotechnology
Abstract

Background Next-generation sequencing technologies have revolutionized the study of small RNAs (sRNAs) on a genome-wide scale. However, classical sRNA library preparation methods introduce serious bias, mainly during adapter ligation steps. Several types of sRNA including plant microRNAs (miRNA), piwi-interacting RNAs (piRNA) in insects, nematodes and mammals, and small interfering RNAs (siRNA) in insects and plants contain a 2’-O-methyl (2’-OMe) modification at their 3′ terminal nucleotide. This inhibits 3′ adapter ligation and makes library preparation particularly challenging. To reduce bias, the NEBNext kit (New England Biolabs) uses polyethylene glycol (PEG), the NEXTflex V2 kit (BIOO Scientific) uses both randomised adapters and PEG, and the novel SMARTer (Clontech) and CATS (Diagenode) kits avoid ligation altogether. Here we compared these methods with Illumina’s classical TruSeq protocol regarding the detection of normal and 2’ OMe RNAs. In addition, we modified the TruSeq and NEXTflex protocols to identify conditions that improve performance. Results Among the five kits tested with their respective standard protocols, the SMARTer and CATS kits had the lowest levels of bias but also had a strong formation of side products, and as a result performed relatively poorly with biological samples; NEXTflex detected the largest numbers of different miRNAs. The use of a novel type of randomised adapters called MidRand-Like (MRL) adapters and PEG improved the detection of 2’ OMe RNAs both in the TruSeq as well as in the NEXTflex protocol. Conclusions While it is commonly accepted that biases in sRNA library preparation protocols are mainly due to adapter ligation steps, the ligation-free protocols were not the best performing methods. Our modified versions of the TruSeq and NEXTflex protocols provide an improved tool for the study of 2’ OMe RNAs. Electronic supplementary material The online version of this article (10.1186/s12864-018-4491-6) contains supplementary material, which is available to authorized users.

Published
2015
Full Text
View/download PDF

18. Characterization of 43 Non-Protein-Coding mRNA Genes in Arabidopsis, Including the MIR162a-Derived Transcripts

Author

Adnane Boualem, Judith Hirsch, Claude Thermes, Martin Crespi, Yves d'Aubenton-Carafa, Marion Vankersschaver, Vincent Lefort, Antoine Lucas, Laboratoire d'Ecophysiologie Moléculaire des Plantes (LEMP), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Institut des sciences du végétal (ISV), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de recherche en génomique végétale (URGV), Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Recherche Agronomique (INRA), Protéines de Protection des Végétaux (PPV), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0106 biological sciences, RNA, Untranslated, Physiology, [SDV]Life Sciences [q-bio], Messenger, Arabidopsis, MESH: Plant Roots, Plant Science, MESH: Base Sequence, MESH: Research Support, Non-U.S. Gov't, Primary transcript, Plant Roots, 01 natural sciences, MESH: RNA, Untranslated, Gene Expression Regulation, Plant, MESH: Sequence Analysis, RNA, MESH: Genes, Plant, MESH: Arabidopsis, Non-U.S. Gov't, Expressed Sequence Tags, Genetics, 0303 health sciences, Expressed sequence tag, MESH: Alternative Splicing, Untranslated, RNA splicing, Sequence Analysis, MESH: Computational Biology, MESH: Mutation, Sequence analysis, Gene prediction, Molecular Sequence Data, Biology, Genes, Plant, Research Support, MESH: Expressed Sequence Tags, 03 medical and health sciences, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, RNA, Messenger, MESH: Gene Expression Regulation, Plant, Gene, MESH: RNA, Messenger, 030304 developmental biology, MESH: Molecular Sequence Data, Base Sequence, Sequence Analysis, RNA, Alternative splicing, Intron, Computational Biology, Plant, Genome Analysis, Alternative Splicing, MicroRNAs, Gene Expression Regulation, Genes, Mutation, RNA, MESH: MicroRNAs, 010606 plant biology & botany
Abstract

Messenger RNAs that do not contain a long open reading frame (ORF) or non-protein-coding RNAs (npcRNAs) are an emerging novel class of transcripts. Their functions may involve the RNA molecule itself and/or short ORF-encoded peptides. npcRNA genes are difficult to identify using standard gene prediction programs that rely on the presence of relatively long ORFs. Here, we used detailed bioinformatic analyses of expressed sequence tag/cDNA databases to detect a restricted set of npcRNAs in the Arabidopsis (Arabidopsis thaliana) genome and further characterized these transcripts using a combination of bioinformatic and molecular approaches. Compositional analyses revealed strong nucleotide strand asymmetries in the npcRNAs, as well as a biased GC content, suggesting the existence of functional constraints on these RNAs. Thirteen of these transcripts display tissue-specific expression patterns, and three are regulated in conditions affecting root architecture. The npcRNA 78 gene contains the miR162 sequence in an alternative intron and corresponds to the MIR162a locus. Although DICER-LIKE 1 (DCL1) mRNA is known to be regulated by miR162-guided cleavage, its level does not change in a mir162a mutant. Alternative splicing of npcRNA 78 leads to several transcript isoforms, which all accumulate in a dcl1 mutant. This suggests that npcRNA 78 is a genuine substrate of DCL1 and that splicing of this microRNA primary transcript and miR162 processing are competitive nuclear events. Our results provide new insights into Arabidopsis npcRNA biology and the potential roles of these genes.

Published
2006
Full Text
View/download PDF

19. Long-Range Correlations in Genomic DNA: A Signature of the Nucleosomal Structure

Author

Yves d'Aubenton-Carafa, Cédric Vaillant, Alain Arneodo, Claude Thermes, Benjamin Audit, J. F. Muzy, Michel, Murielle, Laboratoire Joliot Curie, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Biophysics, General Physics and Astronomy, Biology, 01 natural sciences, Genome, Biophysical Phenomena, 03 medical and health sciences, chemistry.chemical_compound, 0103 physical sciences, Dna bending, Statistical analysis, Dna viral, 010306 general physics, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, DNA, Signature (logic), Nucleosomes, Chromatin, genomic DNA, DNA, Archaeal, Eukaryotic Cells, chemistry, Evolutionary biology, DNA, Viral, Nucleic Acid Conformation
Abstract

We use the ``wavelet transform microscope'' to carry out a comparative statistical analysis of DNA bending profiles and of the corresponding DNA texts. In the three kingdoms, one reveals on both signals a characteristic scale of 100--200 bp that separates two different regimes of power-law correlations (PLC). In the small-scale regime, PLC are observed in eukaryotic, in double-strand DNA viral, and in archaeal genomes, which contrasts with their total absence in the genomes of eubacteria and their viruses. This strongly suggests that small-scale PLC are related to the mechanisms underlying the wrapping of DNA in the nucleosomal structure. We further speculate that the large scale PLC are the signature of the higher-order structure and dynamics of chromatin.

Published
2001
Full Text
View/download PDF

20. A multi-agent system simulating human splice site recognition

Author

Claude Thermes, Laurence Vignal, Frédérique Lisacek, Yves d'Aubenton-Carafa, and Joël Quinqueton

Subjects
Genetics, Genome, Human, RNA Splicing, General Chemical Engineering, Multi-agent system, Intron, Exons, Computational biology, Biology, Applied Microbiology and Biotechnology, Exon, Data sequences, RNA splicing, Humans, Computer Simulation, splice, Biotechnology
Abstract

The present paper describes a method detecting splice sites automatically on the basis of sequence data and models of site/signal recognition supported by experimental evidences. The method is designed to simulate splicing and while doing so, track prediction failures, missing information and possibly test correcting hypotheses. Correlations between nucleotides in the splice site regions and the various elements of the acceptor region are evaluated and combined to assess compensating interactions between elements of the splicing machinery. A scanning model of the acceptor region and a model of interaction between the splicing complexes (exon definition model) are also incorporated in the detection process. Subsets of sites presenting deficiencies of several splice site elements could be identified. Further examination of these sites helps to determine lacking elements and refine models.

Published
1999
Full Text
View/download PDF

21. Two co-existing mechanisms account for the large-scale deletions of mitochondrial DNA in Podospora anserina that involve the 5′ border of a group-II intron

Author

Odile Begel, Yves d'Aubenton-Carafa, and Annie Sainsard-Chanet

Subjects
Mitochondrial DNA, Genes, Fungal, Molecular Sequence Data, Biology, DNA, Mitochondrial, Polymerase Chain Reaction, Podospora anserina, chemistry.chemical_compound, Genetics, Nucleotide, Cloning, Molecular, Sequence Deletion, Recombination, Genetic, chemistry.chemical_classification, Podospora, Base Sequence, Intron, Sequence Analysis, DNA, General Medicine, Group II intron, biology.organism_classification, Molecular biology, Blotting, Southern, chemistry, Nucleic Acid Conformation, DNA, Recombination
Abstract

A degenerative syndrome associated with the accumulation of site-specific deletions within mitochondrial chromosomes occurs in strains of Podospora anserina carrying the AS1-4 nuclear mutation. The site-specific deletion event has been assumed to result from the transposition of a group-II intron (intron alpha) behind an IBS motif, followed by recombination between the two intron repeats. We show here that a number of distinct deletions can accumulate in AS1-4 strains. Most of them are present in low amounts in wild-type cells where they are only detectable in PCR experiments. The deletions can be divided into two classes. In class I, intron alpha is joined to an IBS motif. In class II, the intron is not joined to an IBS site, it can be truncated or contain a few upstream exonic nucleotides; some junctions carry non-templated nucleotides. These results indicate that at least two mechanisms are involved in the generation of large-scale mitochondrial deletions in Podospora. One of them seems to be based on the transposition properties of the group-II alpha intron, the other one on illegitimate recombination. We propose that these two mechanisms use DNA double-strand breaks occurring within the 5' region of intron alpha.

Published
1998
Full Text
View/download PDF

22. Nucleotide composition effects on the long-range correlations in human genes

Author

Emmanuel Bacry, Yves d'Aubenton-Carafa, Alain Arneodo, Benjamin Audit, J. F. Muzy, Claude Thermes, Centre de recherches Paul Pascal (CRPP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Centre de Mathématiques Appliquées (CMAP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Nucleic acid sequence, Intron, Wavelet transform, Biology, Condensed Matter Physics, 01 natural sciences, Electronic, Optical and Magnetic Materials, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Evolutionary biology, 0103 physical sciences, Human genome, 010306 general physics, Gene, ComputingMilieux_MISCELLANEOUS, DNA, GC-content, 030304 developmental biology, Genomic organization
Abstract

We use the wavelet transform to investigate the fractal scaling properties of coding and noncoding human DNA sequences. We find that the strength of the long-range correlations observed in the introns increases with the guanine-cytosine (GC) content, while coding sequences show no such correlations at any GC content. However, we demonstrate that long-range correlations can be detected when the coding sequences are undersampled by retaining the third base of each codon only. This strongly suggests that the observed correlations are not likely to be due to insertion-deletion mechanisms. We comment about the origin of these correlations in terms of putative dynamical processes that could produce the isochore structure of the human genome.

Published
1998
Full Text
View/download PDF

23. High-Frequency Promoter Firing Links THO Complex Function to Heavy Chromatin Formation

Author

Domenico Libri, Sophie Lemoine, Corinne Blugeon, Frédéric Devaux, Mathieu Rougemaille, Yves D'Aubenton‐Carafa, Sebastien Causse, Xavier Darzacq, John Mouaikel, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Plateforme Génomique de l'IBENS, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique des Microorganismes (LGM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Howard Hughes Medical Institute (HHMI), CNRS, Danish National Research Foundation, ANR [ANR-08-Blan-0038-01, ANR 2010-blan-1222-03], Association pour la Recherche sur le Cancer, GenomiqueENS (Genomique ENS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Aarhus University [Aarhus], Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and sophie, lemoine

Subjects
Saccharomyces cerevisiae Proteins, Transcription, Genetic, THO complex, [SDV]Life Sciences [q-bio], Saccharomyces cerevisiae, Biology, DNA-binding protein, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Transcription (biology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene Expression Regulation, Fungal, Promoter Regions, Genetic, lcsh:QH301-705.5, Transcription factor, Gene, ChIA-PET, Heat-Shock Proteins, 030304 developmental biology, 0303 health sciences, 030302 biochemistry & molecular biology, Nuclear Proteins, Promoter, Molecular biology, Chromatin, Cell biology, DNA-Binding Proteins, lcsh:Biology (General), Ribonucleoproteins, Nuclear Pore, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Heat-Shock Response, Transcription Factors
Abstract

International audience; The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single-molecule fluorescence in situ hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase occupancy genome wide. We propose that the THO complex is required for tuning the dynamic of gene-nuclear pore association and mRNP release to the same high pace of transcription initiation.

Published
2013
Full Text
View/download PDF

24. Mitochondrial Intronic Open Reading Frames in Podospora: Mobility and Consecutive Exonic Sequence Variations

Author

Léon Belcour, Michèle Rossignol, Carole H. Sellem, and Yves d'Aubenton-Carafa

Subjects
Genetics, Podospora, Mitochondrial DNA, viruses, Genes, Fungal, Fungi, Reading frame, Intron, Exons, Sequence Analysis, DNA, Investigations, Biology, Gene mutation, biology.organism_classification, DNA, Mitochondrial, Genome, Introns, Open Reading Frames, Exon, ORFS, DNA, Fungal
Abstract

The mitochondrial genome of 23 wild-type strains belonging to three different species of The mitochondrial genome the filamentous fungus Podospora was examined. Among the 15 optional sequences identified are two intronic reading frames, nad1-i4-orf1 and cox1-i7-orf2. We show that the presence of these sequences was strictly correlated with tightly clustered nucleotide substitutions in the adjacent exon. This correlation applies to the presence or absence of closely related open reading frames (ORFs), found at the same genetic locations, in all the Pyrenomycete genera examined. The recent gain of these optional ORFs in the evolution of the genus Podospora probably account for such sequence differences. In the homoplasmic progeny from heteroplasmons constructed between Podospora strains differing by the presence of these optional ORFs, nad1-i4-orf1 and cox1-i7-orf2 appeared highly invasive. Sequence comparisons in the nad1-i4 intron of various strains of the Pyrenomycete family led us to propose a scenario of its evolution that includes several events of loss and gain of intronic ORFs. These results strongly reinforce the idea that group I intronic ORFs are mobile elements and that their transfer, and comcomitant modification of the adjacent exon, could participate in the modular evolution of mitochondrial genomes.

Published
1996
Full Text
View/download PDF

25. Multiscale analysis of genome-wide replication timing profiles using a wavelet-based signal-processing algorithm

Author

Aurélien Rappailles, Olivier Hyrien, Alain Arneodo, Arach Goldar, Guillaume Guilbaud, Yves d'Aubenton-Carafa, Hanna Julienne, Chun-Long Chen, Benjamin Audit, Antoine Baker, Claude Thermes, Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulation transcriptionnelle des génomes (GTR), Département Biologie des Génomes (DBG), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Bergeret, Bernadette, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de génétique moléculaire ( CGM ), Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie de l'ENS Paris (UMR 8197/1024) ( IBENS ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Régulation transcriptionnelle des génomes ( GTR ), Département Biologie des Génomes ( DBG ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie et de Technologies de Saclay ( IBITECS ), and Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA )

Subjects
DNA Replication Timing, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Wavelet Analysis, Computational biology, Biology, DNA replication, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Wavelet, [ PHYS.PHYS.PHYS-BIO-PH ] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Replication (statistics), Humans, Segmentation, 030304 developmental biology, 0303 health sciences, Replication timing, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Genome, Human, Computational biology and bioinformatics, Replication Initiation, Command language, Algorithm, 030217 neurology & neurosurgery, Algorithms, Software, HeLa Cells
Abstract

International audience; In this protocol, we describe the use of the LastWave open-source signal-processing command language (http://perso.ens-lyon.fr/benjamin.audit/LastWave/) for analyzing cellular DNA replication timing profiles. LastWave makes use of a multiscale, wavelet-based signal-processing algorithm that is based on a rigorous theoretical analysis linking timing profiles to fundamental features of the cell's DNA replication program, such as the average replication fork polarity and the difference between replication origin density and termination site density. We describe the flow of signal-processing operations to obtain interactive visual analyses of DNA replication timing profiles. We focus on procedures for exploring the space-scale map of apparent replication speeds to detect peaks in the replication timing profiles that represent preferential replication initiation zones, and for delimiting U-shaped domains in the replication timing profile. In comparison with the generally adopted approach that involves genome segmentation into regions of constant timing separated by timing transition regions, the present protocol enables the recognition of more complex patterns of the spatio-temporal replication program and has a broader range of applications. Completing the full procedure should not take more than 1 h, although learning the basics of the program can take a few hours and achieving full proficiency in the use of the software may take days.

Published
2013
Full Text
View/download PDF

26. From Simple Bacterial and Archaeal Replicons to Replication N/U-Domains

Author

Antoine Baker, Guillaume Guilbaud, Alain Arneodo, Yves d'Aubenton-Carafa, Olivier Hyrien, Chun-Long Chen, Benjamin Audit, Emilie Ma, Arach Goldar, Nataliya Petryk, Malik Kahli, Claude Thermes, Aurélien Rappailles, Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute for Chemistry (MPIC), Max-Planck-Gesellschaft, Régulation transcriptionnelle des génomes (GTR), Département Biologie des Génomes (DBG), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) ( IBENS ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Max Planck Institute for Chemistry ( MPIC ), Régulation transcriptionnelle des génomes ( GTR ), Département Biologie des Génomes ( DBG ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Institut de Biologie et de Technologies de Saclay ( IBITECS ), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Centre de génétique moléculaire ( CGM ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), and Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS)

Subjects
DNA Replication, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Eukaryotic DNA replication, Biology, Pre-replication complex, Origin of replication, History, 21st Century, Genomic Instability, 03 medical and health sciences, Control of chromosome duplication, Minichromosome maintenance, Structural Biology, [ PHYS.PHYS.PHYS-BIO-PH ] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Animals, Humans, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, Mammals, 0303 health sciences, Replication timing, Genome, Bacteria, 030302 biochemistry & molecular biology, Eukaryota, History, 20th Century, Archaea, Licensing factor, Origin recognition complex, Replicon
Abstract

The Replicon Theory proposed 50 years ago has proven to apply for replicons of the three domains of life. Here, we review our knowledge of genome organization into single and multiple replicons in bacteria, archaea and eukarya. Bacterial and archaeal replicator/initiator systems are quite specific and efficient, whereas eukaryotic replicons show degenerate specificity and efficiency, allowing for complex regulation of origin firing time. We expand on recent evidence that ~50% of the human genome is organized as ~1,500 megabase-sized replication domains with a characteristic parabolic (U-shaped) replication timing profile and linear (N-shaped) gradient of replication fork polarity. These N/U-domains correspond to self-interacting segments of the chromatin fiber bordered by open chromatin zones and replicate by cascades of origin firing initiating at their borders and propagating to their center, possibly by fork-stimulated initiation. The conserved occurrence of this replication pattern in the germline of mammals has resulted over evolutionary times in the formation of megabase-sized domains with an N-shaped nucleotide compositional skew profile due to replication-associated mutational asymmetries. Overall, these results reveal an evolutionarily conserved but developmentally plastic organization of replication that is driving mammalian genome evolution.

Published
2013
Full Text
View/download PDF

27. Megabase replication domains along the human genome: relation to chromatin structure and genome organisation

Author

Benjamin, Audit, Lamia, Zaghloul, Antoine, Baker, Alain, Arneodo, Chun-Long, Chen, Yves, d'Aubenton-Carafa, and Claude, Thermes

Subjects
DNA Replication, Histones, Structure-Activity Relationship, Gene Expression Regulation, Models, Genetic, Genome, Human, Protein Conformation, Humans, Nucleic Acid Conformation, Replication Origin, DNA, Regulatory Sequences, Nucleic Acid, Chromatin Assembly and Disassembly
Abstract

In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

Published
2012

28. Linking the DNA strand asymmetry to the spatio-temporal replication program

Author

Claude Thermes, Yves d'Aubenton-Carafa, Chun-Long Chen, Benjamin Audit, Alain Arneodo, Hanna Julienne, Antoine Baker, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Lyon, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
DNA Replication, Transcription, Genetic, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Biophysics, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Spatio-Temporal Analysis, Transcription (biology), 0103 physical sciences, Animals, Humans, General Materials Science, Nucleotide, 010306 general physics, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Models, Genetic, Substitution (logic), DNA, Surfaces and Interfaces, General Chemistry, Kinetics, chemistry, CpG site, Human genome, Cytosine, Biotechnology
Abstract

In paper I, we addressed the impact of the spatio-temporal program on the DNA composition evolution in the case of time homogeneous and neighbor-independent substitution rates. But substitution rates do depend on the flanking nucleotides as exemplified in vertebrates where CpG sites are hypermutable so that the substitution rate C --> T depends dramatically (ten fold) on whether the cytosine belongs to a CG dinucleotide or not. With the specific goal to account for neighbor-dependence, we revisit our minimal modeling of neutral substitution rates in the human genome. When assuming that r = CpG --> TpG and its reverse complement r(c) = CpG --> CpA are (by far) the main neighbor-dependent substitution rates, we demonstrate, using perturbative analysis, that neighbor-dependence does not affect the decomposition of the compositional asymmetry into a transcription- and a replication-associated components, the former increases in magnitude with transcription rate and changes sign with gene orientation, whereas the latter is proportional to the replication fork polarity. Indeed the neighbor dependence case differs from the neighbor-independent model by an additional source term related to the CG dinucleotide content in both the transcription and replication-associated components. We finally discuss the case of time-dependent substitution rates confirming as a very general result the fact that the skew can still be decomposed into a transcription- and a replication-associated components.

Published
2012
Full Text
View/download PDF

29. Megabase Replication Domains Along the Human Genome: Relation to Chromatin Structure and Genome Organisation

Author

Claude Thermes, Lamia Zaghloul, Antoine Baker, Chun-Long Chen, Benjamin Audit, Alain Arneodo, and Yves d'Aubenton-Carafa

Subjects
Genetics, Genome evolution, Evolutionary biology, DNA replication, Human genome, Genome project, Biology, Origin of replication, Genome, Chromatin, Chromatin Fiber
Abstract

In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

Published
2012
Full Text
View/download PDF

30. In vivo SELEX reveals novel sequence and structural determinants of Nrd1-Nab3-Sen1-dependent transcription termination

Author

Odil, Porrua, Fruzsina, Hobor, Jocelyne, Boulay, Karel, Kubicek, Yves, D'Aubenton-Carafa, Rajani Kanth, Gudipati, Richard, Stefl, and Domenico, Libri

Subjects
Saccharomyces cerevisiae Proteins, Amino Acid Motifs, Molecular Sequence Data, SELEX Aptamer Technique, DNA Helicases, Nuclear Proteins, RNA-Binding Proteins, Saccharomyces cerevisiae, Article, Gene Expression Regulation, Fungal, Transcription Termination, Genetic, Amino Acid Sequence, RNA Helicases, Protein Binding
Abstract

The Nrd1-Nab3-Sen1 (NNS) complex pathway is responsible for transcription termination of cryptic unstable transcripts and sn/snoRNAs. The NNS complex recognizes short motifs on the nascent RNA, but the presence of these sequences alone is not sufficient to define a functional terminator. We generated a homogeneous set of several hundreds of artificial, NNS-dependent terminators with an in vivo selection approach. Analysis of these terminators revealed novel and extended sequence determinants for transcription termination and NNS complex binding as well as supermotifs that are critical for termination. Biochemical and structural data revealed that affinity and specificity of RNA recognition by Nab3p relies on induced fit recognition implicating an α-helical extension of the RNA recognition motif. Interestingly, the same motifs can be recognized by the NNS or the mRNA termination complex depending on their position relative to the start of transcription, suggesting that they function as general transcriptional insulators to prevent interference between the non-coding and the coding yeast transcriptomes.

Published
2012

31. BRASERO: A resource for benchmarking RNA secondary structure comparison algorithms

Author

Hélène Touzet, Cedric Chauve, Cédric Saule, Claude Thermes, Christine Drevet, Antoine de Monte, Yves d'Aubenton-Carafa, Fabrice Leclerc, Aïda Ouangraoua, Alain Denise, Marie-France Sagot, Michel Termier, Pascal Ferraro, Claire Herrbach, Julien Allali, Daniel Gautheret, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Algorithms and Models for Integrative Biology (AMIB ), Laboratoire d'informatique de l'École polytechnique [Palaiseau] (LIX), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Department of Mathematics [Burnaby] (SFU), Simon Fraser University (SFU.ca), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et microbiologie [Orsay] (IGM), Pacific Institute for the Mathematical Sciences (PIMS), University of Calgary, Maturation des ARN et enzymologie moléculaire (MAEM), Cancéropôle du Grand Est-Université Henri Poincaré - Nancy 1 (UHP)-IFR111-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Bioinformatics and Sequence Analysis (BONSAI), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria), An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Recherche en Informatique (LRI), and University of Calgary-Centre National de la Recherche Scientifique (CNRS)

Subjects
Computer science, Biomedical Engineering, 0102 computer and information sciences, computer.software_genre, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), Genome, Nucleic acid secondary structure, [SPI]Engineering Sciences [physics], 03 medical and health sciences, Software, [CHIM]Chemical Sciences, [INFO]Computer Science [cs], lcsh:QH301-705.5, lcsh:Statistics, lcsh:HA1-4737, 030304 developmental biology, Resource Review, 0303 health sciences, business.industry, RNA, Benchmarking, Non-coding RNA, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, ComputingMethodologies_PATTERNRECOGNITION, lcsh:Biology (General), 010201 computation theory & mathematics, Pairwise comparison, Edit distance, Data mining, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer, MathematicsofComputing_DISCRETEMATHEMATICS
Abstract

No comment; International audience; The pairwise comparison of RNA secondary structures is a fundamental problem, with direct application in mining databases for annotating putative noncoding RNA candidates in newly sequenced genomes. An increasing number of software tools are available for comparing RNA secondary structures, based on different models (such as ordered trees or forests, arc annotated sequences, and multilevel trees) and computational principles (edit distance, alignment). We describe here the website BRASERO that offers tools for evaluating such software tools on real and synthetic datasets. Copyright © 2012 Julien Allali et al.

Published
2012
Full Text
View/download PDF

32. Linking the DNA strand asymmetry to the spatio-temporal replication program I. About the role of the replication fork polarity in genome evolution

Author

Hanna Julienne, Antoine Baker, Chun-Long Chen, Benjamin Audit, Claude Thermes, Alain Arneodo, Yves d'Aubenton-Carafa, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
DNA Replication, Genome evolution, Transcription, Genetic, media_common.quotation_subject, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Biophysics, Genome, Asymmetry, Evolution, Molecular, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Spatio-Temporal Analysis, Mutation Rate, Transcription (biology), Humans, General Materials Science, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, media_common, Physics, 0303 health sciences, Replication timing, Models, Genetic, Genome, Human, Surfaces and Interfaces, General Chemistry, DNA, chemistry, Evolutionary biology, Human genome, 030217 neurology & neurosurgery, Biotechnology, HeLa Cells
Abstract

Two key cellular processes, namely transcription and replication, require the opening of the DNA double helix and act differently on the two DNA strands, generating different mutational patterns (mutational asymmetry) that may result, after long evolutionary time, in different nucleotide compositions on the two DNA strands (compositional asymmetry). We elaborate on the simplest model of neutral substitution rates that takes into account the strand asymmetries generated by the transcription and replication processes. Using perturbation theory, we then solve the time evolution of the DNA composition under strand-asymmetric substitution rates. In our minimal model, the compositional and substitutional asymmetries are predicted to decompose into a transcription- and a replication-associated components. The transcription-associated asymmetry increases in magnitude with transcription rate and changes sign with gene orientation while the replication-associated asymmetry is proportional to the replication fork polarity. These results are confirmed experimentally in the human genome, using substitution rates obtained by aligning the human and chimpanzee genomes using macaca and orangutan as outgroups, and replication fork polarity determined in the HeLa cell line as estimated from the derivative of the mean replication timing. When further investigating the dynamics of compositional skew evolution, we show that it is not at equilibrium yet and that its evolution is an extremely slow process with characteristic time scales of several hundred Myrs.

Published
2012
Full Text
View/download PDF

33. Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines

Author

Chun-Long Chen, Benjamin Audit, Guillaume Guilbaud, Arach Goldar, Yves d'Aubenton-Carafa, Alain Arneodo, Antoine Baker, Olivier Hyrien, Cédric Vaillant, Benoit Moindrot, Claude Thermes, Fabien Mongelard, Antoine Leleu, Aurélien Rappailles, Laboratoire Joliot Curie, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche under project REFOPOL (ANR 10 BLAN 1615 01), and by grants from the Fondation pour la Recherche Médicale (équipe labélisée), the ARC and the Ligue contre le Cancer (Comité de Paris) to O.H. A.R was supported by the ANR NT05-3_41825 and by a fellowship from the Conseil Regional d'Ile de France (DIM STEM-Pôle), G.G. was supported by the Ministère de l'Education Nationale de l'Enseignement Supérieur et de la Recherche, and by the Association pour la Recherche sur le Cancer., École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Autard, Delphine

Subjects
DNA Replication, Molecular Sequence Data, Biophysics, Replication Origin, Pre-replication complex, Cell Line, DNA replication factor CDT1, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Minichromosome maintenance, Control of chromosome duplication, Nucleic Acids, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, SDV:BBM, Genetics, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Computer Simulation, Molecular Biology, Biology, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Replication timing, Genome, Ecology, biology, Base Sequence, Models, Genetic, Genome, Human, Physics, DNA replication, Chromosome Mapping, Computational Biology, DNA, Genomics, Cell biology, Licensing factor, Computational Theory and Mathematics, lcsh:Biology (General), Modeling and Simulation, biology.protein, Origin recognition complex, Epigenetics, 030217 neurology & neurosurgery, Research Article
Abstract

In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome., Author Summary DNA replication in human cells requires the parallel progression along the genome of thousands of replication machineries. Comprehensive knowledge of genetic inheritance at different development stages relies on elucidating the mechanisms that regulate the location and progression of these machineries throughout the duration of the DNA synthetic phase of the cell cycle. Here, we determine in multiple human cell types the existence of a new type of megabase-sized replication domains across which the average orientation of the replication machinery changes in a linear manner. These domains are revealed in 7 somatic cell types by a U-shaped pattern in the replication timing profiles as well as by N-shaped patterns in the DNA compositional asymmetry profile reflecting the existence of a replication-associated mutational asymmetry in the germline. These domains therefore correspond to a robust mode of replication across cell types and during evolution. Using genome-wide data on the frequency of interaction of distant chromatin segments in two cell lines, we find that these U/N-replication domains remarkably correspond to self-interacting folding units of the chromatin fiber.

Published
2012
Full Text
View/download PDF

34. Evidence for Sequential and Increasing Activation of Replication Origins along Replication Timing Gradients in the Human Genome

Author

Alain Arneodo, Guillaume Guilbaud, Arach Goldar, Olivier Hyrien, Antoine Baker, Claude Thermes, Yves d'Aubenton-Carafa, Chun-Long Chen, Benjamin Audit, Aurélien Rappailles, Autard, Delphine, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, The Jacques-Monod Institute flow cytometry platform, UMR CNRS 7592, University Paris VII is supported by the Région Ile-de-France, contract number E539 and La Ligue Nationale contre le Cancer (Comité Ile de France), contract number R03/75-79. This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Agence Nationale de la Recherche (NT05-3_41825 and 10 BLAN 1615 01) and grants from the Association pour la Recherche sur le Cancer, the Ligue Contre le Cancer (Comité de Paris) and the Fondation pour la Recherche Médicale (équipe labellisée) to O.H. A.R was supported by the ANR NT05-3_41825 and by a fellowship from the Conseil Regional d'Ile de France (DIM STEM-Pôle), G.G. was supported by the Ministère de l'Education Nationale de l'Enseignement Supérieur et de la Recherche, and by the Association pour la Recherche sur le Cancer., École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Time Factors, Cell Separation, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Molecular Cell Biology, Genome Sequencing, lcsh:QH301-705.5, Mathematical Computing, Genetics, 0303 health sciences, Ecology, Physics, Statistics, Genomics, Genome Scans, Flow Cytometry, Chromatin, Cell biology, Functional Genomics, Nucleic acids, Computational Theory and Mathematics, Genetic Techniques, Modeling and Simulation, Interdisciplinary Physics, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Sequence Analysis, Research Article, DNA Replication, Biophysics, Replication Origin, Saccharomyces cerevisiae, Biology, Biostatistics, Origin of replication, 03 medical and health sciences, Cellular and Molecular Neuroscience, Genome Analysis Tools, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Replication (statistics), Humans, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Replication timing, Models, Statistical, Models, Genetic, Genome, Human, DNA replication, Computational Biology, DNA, Sequence Analysis, DNA, Kinetics, chemistry, lcsh:Biology (General), Human genome, Structural Genomics, 030217 neurology & neurosurgery, Mathematics, HeLa Cells
Abstract

Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general model for their replication kinetics., Author Summary Eukaryotic chromosomes replicate from multiple replication origins that fire at different times in S phase. The mechanisms that specify origin position and firing time and coordinate origins to ensure complete genome duplication are unclear. Previous studies proposed either that origins are arranged in temporally coordinated groups or fire independently of each other in a stochastic manner. Here, we have performed a quantitative analysis of human genome replication kinetics using a combination of DNA combing, which reveals local patterns of origin firing and replication fork progression on single DNA molecules, and massive sequencing of newly replicated DNA, which reveals the population-averaged replication timing profile of the entire genome. We show that origins are activated synchronously in large regions of uniform replication timing but more gradually in temporal transition regions and that the rate of origin firing increases as replication progresses. Large regions of unidirectional fork progression are abundant in embryonic stem cells but rare in differentiated cells. We propose a model in which replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA in a manner that explains the shape of the replication timing profile. These results provide a fundamental insight into the temporal regulation of mammalian genome replication.

Published
2011
Full Text
View/download PDF

35. The Dogfish Scyliorhinus canicula: A Reference in Jawed Vertebrates

Author

Marion Coolen, Sébastien Henry, Patrick Wincker, Frédérick Gavory, Sylvie Mazan, Claude Thermes, Claudia Compagnucci, Pascal Sourdaine, Laurent Lévêque, Danièle Chassoux, Corinne Da Silva, Arnaud Menuet, Sylvie Samain, Michael J. Depew, Gavin J. P. Naylor, Yves d'Aubenton-Carafa, and Isabel Rodríguez-Moldes

Subjects
Phylogenetic tree, Spotted dogfish, biology, Extant taxon, Evolutionary biology, Evolutionary developmental biology, Scyliorhinus canicula, Context (language use), Comparative anatomy, biology.organism_classification, General Biochemistry, Genetics and Molecular Biology, Organism
Abstract

INTRODUCTIONDue to their large size and long generation times, chondrichthyans have been largely ignored by geneticists. However, their key phylogenetic position makes them ideal subjects to study the molecular bases of the important morphological and physiological innovations that characterize jawed vertebrates. Such analyses are crucial to understanding the origin of the complex genetic mechanisms unraveled in osteichthyans. The small spotted dogfish Scyliorhinus canicula, a representative of the largest order of extant sharks, presents a number of advantages in this context. Due to its relatively small size among sharks, its abundance, and easy maintenance, the dogfish has been an important model in comparative anatomy and physiology for more than a century. Recently, revived interest has occurred with the development of large-scale transcriptomic and genomic resources, together with the establishment of facilities allowing massive egg and embryo production. These new tools open the way to molecular analyses of the elaborate physiological and sensory systems used by sharks. They also make it possible to take advantage of unique characteristics of these species, such as organ zonation, in analyses of cell proliferation and differentiation. Finally, they offer important perspectives to evolutionary developmental biology that will provide a better understanding of the origin and diversifications of jawed vertebrates. The dogfish whole-genome sequence, which may shortly become accessible, should establish this species as an essential shark reference, complementary to other chondrichthyan models. These analyses are likely to reveal an organism of an underestimated complexity, far from the primitive prototypical gnathostome anticipated in gradistic views.

Published
2011

36. Multi-scale coding of genomic information: From DNA sequence to genome structure and function

Author

Cédric Vaillant, Claude Thermes, Françoise Argoul, Benjamin Audit, Yves d'Aubenton-Carafa, Alain Arneodo, Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physics, 0303 health sciences, DNA sequence Chromatin Nucleosome Genome organization Epigenetics Transcription Replication Compositional strand asymmetry Statistical physics Hetero-polymer Generalized worm-like-chain model Scale-invariance Multi-fractal Multi-scale analysis Wavelet transform Long-range correlations Atomic force microscopy, General Physics and Astronomy, Nanotechnology, Computational biology, 01 natural sciences, Genome, DNA sequencing, Chromatin, 03 medical and health sciences, chemistry.chemical_compound, chemistry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 0103 physical sciences, DECIPHER, Nucleosome, 010306 general physics, Gene, DNA, 030304 developmental biology, Genomic organization
Abstract

International audience; Understanding how chromatin is spatially and dynamically organized in the nucleus of eukaryotic cells and how this affects genome functions is one of the main challenges of cell biology. Since the different orders of packaging in the hierarchical organization of DNA condition the accessibility of DNA sequence elements to trans-acting factors that control the transcription and replication processes, there is actually a wealth of structural and dynamical information to learn in the primary DNA sequence. In this review, we show that when using concepts, methodologies, numerical and experimental techniques coming from statistical mechanics and nonlinear physics combined with wavelet-based multi-scale signal processing, we are able to decipher the multi-scale sequence encoding of chromatin condensation–decondensation mechanisms that play a fundamental role in regulating many molecular processes involved in nuclear functions.

Published
2011
Full Text
View/download PDF

37. Replication-Associated Mutational Asymmetry in the Human Genome

Author

Olivier Hyrien, Alain Arneodo, Guillaume Guilbaud, Maxime Huvet, Claude Thermes, Yves d'Aubenton-Carafa, Lauranne Duquenne, Chun-Long Chen, Benjamin Audit, Antoine Baker, Aurélien Rappailles, Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Lyon, Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Régulation de l'expression génétique (REG), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
DNA Replication, Genome evolution, DNA polymerase, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Cell Line, Evolution, Molecular, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Genetics, Humans, Molecular Biology, Ecology, Evolution, Behavior and Systematics, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Base Composition, 0303 health sciences, Replication timing, Models, Genetic, biology, Genome, Human, DNA replication, Germ Cells, chemistry, Organ Specificity, Replication Initiation, Evolutionary biology, Mutation, biology.protein, DNA mismatch repair, Human genome, K562 Cells, 030217 neurology & neurosurgery, DNA, HeLa Cells
Abstract

During evolution, mutations occur at rates that can differ between the two DNA strands. In the human genome, nucleotide substitutions occur at different rates on the transcribed and non-transcribed strands that may result from transcription-coupled repair. These mutational asymmetries generate transcription-associated compositional skews. To date, the existence of such asymmetries associated with replication has not yet been established. Here, we compute the nucleotide substitution matrices around replication initiation zones identified as sharp peaks in replication timing profiles and associated with abrupt jumps in the compositional skew profile. We show that the substitution matrices computed in these regions fully explain the jumps in the compositional skew profile when crossing initiation zones. In intergenic regions, we observe mutational asymmetries measured as differences between complementary substitution rates; their sign changes when crossing initiation zones. These mutational asymmetries are unlikely to result from cryptic transcription but can be explained by a model based on replication errors and strand-biased repair. In transcribed regions, mutational asymmetries associated with replication superimpose on the previously described mutational asymmetries associated with transcription. We separate the substitution asymmetries associated with both mechanisms, which allows us to determine for the first time in eukaryotes, the mutational asymmetries associated with replication and to reevaluate those associated with transcription. Replication-associated mutational asymmetry may result from unequal rates of complementary base misincorporation by the DNA polymerases coupled with DNA mismatch repair (MMR) acting with different efficiencies on the leading and lagging strands. Replication, acting in germ line cells during long evolutionary times, contributed equally with transcription to produce the present abrupt jumps in the compositional skew. These results demonstrate that DNA replication is one of the major processes that shape human genome composition.

Published
2011
Full Text
View/download PDF

38. Evolution of Hox gene clusters in gnathostomes: insights from a survey of a shark (Scyliorhinus canicula) transcriptome

Author

Sylvie Bernard-Samain, Mélanie Debiais-Thibaud, Sylvie Mazan, Didier Casane, Silvan Oulion, Claude Thermes, Yves d'Aubenton-Carafa, Patrick Wincker, Corinne Da Silva, Frédéric Gavory, Laboratoire Evolution, Génomes et Spéciation (LEGS), Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Station biologique de Roscoff (SBR), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Molecular Sequence Data, Biology, Homology (biology), shark, Evolution, Molecular, 03 medical and health sciences, Exon, 0302 clinical medicine, Scyliorhinus canicula, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Gene cluster, Genetics, Animals, Amino Acid Sequence, Hox gene, Molecular Biology, Gene, gnathostomes, Ecology, Evolution, Behavior and Systematics, Phylogeny, 030304 developmental biology, Gene Library, Expressed Sequence Tags, Homeodomain Proteins, 0303 health sciences, Expressed sequence tag, Base Sequence, cDNA library, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Gene Expression Profiling, Alternative splicing, Genes, Homeobox, Chromosome Mapping, Exons, Multigene Family, Sharks, Hox gene cluster, transcriptome, 030217 neurology & neurosurgery
Abstract

International audience; It is now well established that there were four Hox gene clusters in the genome of the last common ancestor of extant gnathostomes. To better understand the evolution of the organization and expression of these genomic regions, we have studied the Hox gene clusters of a shark (Scyliorhinus canicula). We sequenced 225,580 expressed sequence tags from several embryonic cDNA libraries. Blast searches identified corresponding transcripts to almost all the HoxA, HoxB, and HoxD cluster genes. No HoxC transcript was identified, suggesting that this cluster is absent or highly degenerate. Using Hox gene sequences as probes, we selected and sequenced seven clones from a bacterial artificial chromosome library covering the complete region of the three gene clusters. Mapping of cDNAs to these genomic sequences showed extensive alternative splicing and untranslated exon sharing between neighboring Hox genes. Homologous noncoding exons could not be identified in transcripts from other species using sequence similarity. However, by comparing conserved noncoding sequences upstream of these exons in different species, we were able to identify homology between some exons. Some alternative splicing variants are probably very ancient and were already coded for by the ancestral Hox gene cluster. We also identified several transcripts that do not code for Hox proteins, are probably not translated, and all but one are in the reverse orientation to the Hox genes. This survey of the transcriptome of the Hox gene clusters of a shark shows that the high complexity observed in mammals is a gnathostome ancestral feature.

Published
2010
Full Text
View/download PDF

39. A novel strategy of transcription regulation by intragenic nucleosome ordering

Author

Alain Arneodo, Yves d'Aubenton-Carafa, Claude Thermes, Leonor Palmeira, Benjamin Audit, Cédric Vaillant, Guillaume Chevereau, Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Letter, Saccharomyces cerevisiae Proteins, Transcription, Genetic, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Genes, Fungal, Saccharomyces cerevisiae, Biology, Chromatin remodeling, 03 medical and health sciences, 0302 clinical medicine, Gene Expression Regulation, Fungal, Histone methylation, Genetics, Transcriptional regulation, Nucleosome, Gene, Genetics (clinical), ChIA-PET, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Chromatin, Cell biology, Nucleosomes, Thermodynamics, Transcription Initiation Site, Crystallization, 030217 neurology & neurosurgery
Abstract

Numerous studies of chromatin structure showed that nucleosome free regions (NFRs) located at 5′ gene ends contribute to transcription initiation regulation. Here, we determine the role of intragenic chromatin structure on gene expression regulation. We show that, along Saccharomyces cerevisiae genes, nucleosomes are highly organized following two types of architecture that depend only on the distance between the NFRs located at the 5′ and 3′ gene ends. In the first type, this distance constrains in vivo the positioning of n nucleosomes regularly organized in a “crystal-like” array. In the second type, this distance is such that the corresponding genes can accommodate either n or (n + 1) nucleosomes, thereby displaying two possible crystal-like arrays of n weakly compacted or n + 1 highly compacted nucleosomes. This adaptability confers “bi-stable” properties to chromatin and is a key to its dynamics. Compared to crystal-like genes, bi-stable genes present higher transcriptional plasticity, higher sensitivity to chromatin regulators, higher H3 turnover rate, and lower H2A.Z enrichment. The results strongly suggest that transcription elongation is facilitated by higher chromatin compaction. The data allow us to propose a new paradigm of transcriptional control mediated by the stability and the level of compaction of the intragenic chromatin architecture and open new ways for investigating eukaryotic gene expression regulation.

Published
2010
Full Text
View/download PDF

40. Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes

Author

Aurélien Rappailles, Claude Thermes, Chun-Long Chen, Benjamin Audit, Laurent Farinelli, Alain Arneodo, Guillaume Guilbaud, Yves d'Aubenton-Carafa, Lauranne Duquenne, Maxime Huvet, Olivier Hyrien, Bioinformatique, phylogénie et génomique évolutive (BPGE), Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Régulation de l'expression génétique (REG), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)

Subjects
DNA Replication, Genome evolution, Pan troglodytes, DNA Replication Timing, DNA repair, [SDV]Life Sciences [q-bio], Mutation, Missense, Replication, Biology, genome evolution, medicine.disease_cause, Genome, Evolution, Molecular, Mice, 03 medical and health sciences, 0302 clinical medicine, Pongo pygmaeus, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Animals, Humans, Genetics (clinical), 030304 developmental biology, Mammals, 0303 health sciences, Mutation, Replication timing, Genome, Human, Research, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Rats, CpG site, DNA methylation, Macaca, CpG Islands, Drosophila, Human genome, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030217 neurology & neurosurgery, HeLa Cells
Abstract

International audience; Neutral nucleotide substitutions occur at varying rates along genomes, and it remains a major issue to unravel the mechanisms that cause these variations and to analyze their evolutionary consequences. Here, we study the role of replication in the neutral substitution pattern. We obtained a high-resolution replication timing profile of the whole human genome by massively parallel sequencing of nascent BrdU-labeled replicating DNA. These data were compared to the neutral substitution rates along the human genome, obtained by aligning human and chimpanzee genomes using macaque and orangutan as outgroups. All substitution rates increase monotonously with replication timing even after controlling for local or regional nucleotide composition, crossover rate, distance to telomeres, and chromatin compaction. The increase in non-CpG substitution rates might result from several mechanisms including the increase in mutation-prone activities or the decrease in efficiency of DNA repair during the S phase. In contrast, the rate of C --> T transitions in CpG dinucleotides increases in later-replicating regions due to increasing DNA methylation level that reflects a negative correlation between timing and gene expression. Similar results are observed in the mouse, which indicates that replication timing is a main factor affecting nucleotide substitution dynamics at non-CpG sites and constitutes a major neutral process driving mammalian genome evolution.

Published
2010
Full Text
View/download PDF

41. Wavelet-based method to disentangle transcription- and replication-associated strand asymmetries in mammalian genomes

Author

Benjamin Audit, Lamia Zaghloul, Yves d'Aubenton-Carafa, Alain Arneodo, Claude Thermes, Samuel Nicolay, Antoine Baker, Université de Lyon, Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Genome evolution, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Replication, Computational biology, DNA sequences, Origin of replication, Bioinformatics, 01 natural sciences, Genome, DNA sequencing, 03 medical and health sciences, chemistry.chemical_compound, Transcription (biology), 0103 physical sciences, 010306 general physics, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Mathematics, Continuous wavelet transform, Mammalian genomes, 0303 health sciences, Applied Mathematics, chemistry, Human genome, Strand compositional asymmetry, Transcription, DNA
Abstract

During genome evolution, the two strands of the DNA double helix are not subjected to the same mutation patterns. This mutation bias is considered as a by-product of replicative and transcriptional activities. In this paper, we develop a wavelet-based methodology to analyze the DNA strand asymmetry profiles with the specific goal to extract the contributions associated with replication and transcription respectively. In a first step, we use an adapted N-shaped analyzing wavelet to perform a multi-scale pattern recognition analysis of the sum of the TA and GC skews along human chromosomes. This method provides an objective segmentation of the human genome in skew domains of ≃ 1 Mbp characteristic size, bordered by two putative replication origins recognized as large amplitude upward jumps in the noisy skew profile. In a second step, we use a least-square fitting procedure to disentangle, in these skew domains, the small-scale (the mean human gene size ≃ 30 kbp ) square-like transcription component from the global N-shaped component induced by replication. When applying this procedure to the 22 human autosomes, we delineate 678 replication domains of mean length L ¯ = 1.2 ± 0.6 Mbp spanning 33.8% of the human genome and we predict 1062 replication origins. When investigating the distribution of transcription-associated skew inside the replication N-domains, we reveal some dependence upon the distance to the putative replication origins located at N-domain extremities, the closer the genes to the origin, the larger their transcription bias as the signature of a higher transcriptional activity in the germ-line. As a comparative analysis, we further apply our wavelet-based methodology to skew profiles along the mouse chromosomes. The striking similarity of the results in human and mouse indicates that the remarkable gene organization observed inside the human replication N-domains is likely to be a general feature of mammalian genomes.

Published
2010
Full Text
View/download PDF

42. Open chromatin encoded in DNA sequence is the signature of 'master' replication origins in human cells

Author

Yves d'Aubenton-Carafa, Benjamin Audit, Alain Arneodo, Lamia Zaghloul, Guillaume Chevereau, Cédric Vaillant, Claude Thermes, Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Lyon, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
DNA re-replication, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Replication Origin, Biology, Origin of replication, 03 medical and health sciences, 0302 clinical medicine, Control of chromosome duplication, Chromosomal Instability, Genetics, Nucleosome, Deoxyribonuclease I, Humans, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Base Sequence, Chromosome Mapping, Genomics, DNA, DNA Methylation, Chromatin, Evolutionary biology, Origin recognition complex, Human genome, Transcription Initiation Site, 030217 neurology & neurosurgery
Abstract

For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions approximately 300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as 'master' replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these 'master' origins are likely to play a key role in genome dynamics during evolution and in pathological situations.

Published
2009
Full Text
View/download PDF

43. Neurodevelopment genes in lampreys reveal trends for forebrain evolution in craniates

Author

Yves d'Aubenton-Carafa, Emna Marrakchi, Patrick Wincker, Sylvie Mazan, Adèle Guérin, Corinne Da Silva, Sylvie Rétaux, Développement, évolution et plasticité du système nerveux (DEPSN), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Centre de génétique moléculaire (CGM), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
Body Patterning, Neurogenesis, ved/biology.organism_classification_rank.species, Marine and Aquatic Sciences, lcsh:Medicine, Molecular Biology/Molecular Evolution, Biology, Evolutionary Biology/Developmental Evolution, 03 medical and health sciences, Prosencephalon, 0302 clinical medicine, Proliferating Cell Nuclear Antigen, biology.animal, Developmental Biology/Developmental Molecular Mechanisms, Animals, Model organism, lcsh:Science, Zebrafish, Embryonic Stem Cells, In Situ Hybridization, Phylogeny, Cell Proliferation, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Models, Genetic, ved/biology, Lamprey, lcsh:R, Gene Expression Regulation, Developmental, Lampreys, Vertebrate, Gnathostomata, Anatomy, biology.organism_classification, Biological Evolution, Developmental Biology/Neurodevelopment, Evolutionary biology, Vertebrates, Forebrain, lcsh:Q, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Developmental Biology/Developmental Evolution, 030217 neurology & neurosurgery, Research Article, Signal Transduction
Abstract

International audience; The forebrain is the brain region which has undergone the most dramatic changes through vertebrate evolution. Analyses conducted in lampreys are essential to gain insight into the broad ancestral characteristics of the forebrain at the dawn of vertebrates, and to understand the molecular basis for the diversifications that have taken place in cyclostomes and gnathostomes following their splitting. Here, we report the embryonic expression patterns of 43 lamprey genes, coding for transcription factors or signaling molecules known to be involved in cell proliferation, stemcellness, neurogenesis, patterning and regionalization in the developing forebrain. Systematic expression patterns comparisons with model organisms highlight conservations likely to reflect shared features present in the vertebrate ancestors. They also point to changes in signaling systems -pathways which control the growth and patterning of the neuroepithelium-, which may have been crucial in the evolution of forebrain anatomy at the origin of vertebrates.

Published
2009
Full Text
View/download PDF

44. Determination of an RNA structure involved in splicing inhibition of a muscle-specific exon

Author

Edward Brody, Béatrice Clouet d’Orval, Yves d'Aubenton-Carafa, and Joëlle Marie

Subjects
RNase P, RNA Splicing, Molecular Sequence Data, Restriction Mapping, Exonic splicing enhancer, Tropomyosin, Biology, Exon, Exon trapping, Structural Biology, Organometallic Compounds, RNA Precursors, Animals, RNA, Messenger, Molecular Biology, Splice site mutation, Base Sequence, Muscles, Intron, RNA, DNA, Exons, Molecular biology, Models, Chemical, Mutation, RNA splicing, Nucleic Acid Conformation, Chickens
Abstract

We have investigated the RNA structure of the region surrounding the muscle-specific exon 6B of the chicken β-tropomyosin gene. We have used a variety of chemical and enzymatic probes: dimethylsulfate, N-cyclohexyl-N′-(2-(N′-methylmorpholino)-ethyl)-carbodiimide-p-toluenesulfonate), RNase T1 and RNase V1. Lead acetate was also used to obtain some information on the tertiary structure of this region. Probing the wild-type sequence suggests a model involving one-stem and three-stem-loop structures in and around this exon. Two of these, hairpin I and stem III, have previously been implicated in repression of splicing of the intron following exon 6B in a HeLa nuclear extract. Stem I includes sequences at the beginning of exon 6B and stem III results from interaction of the intron upstream from exon 6B with sequences in the middle of the intron downstream from this exon (the intron whose splicing is repressed). Neither stem I nor stem III directly involves the consensus sequences (5′ splice site, branch-point, 3′ splice site) of the repressed intron. Probing RNAs that are derepressed for splicing of this intron show that there are structural changes around the 5′ splice site and branch-point sequence that correlate with the derepression. This is true, despite the fact that the derepressed RNAs are altered in a region far from these consensus sequences. The most striking structural correlation with splicing capacity of the intron downstream from exon 6B is seen by probing with lead acetate. Lead ions cut RNA at specific residues; these sites are very sensitive to RNA tertiary structure. Repressed and derepressed RNAs show entirely different cleavage patterns after incubation with lead acetate. Remarkably, hybridizing a derepressed RNA with an RNA comprising the ascending arm of stem III not only re-establishes repression, but also converts the pattern of susceptibility to attack by lead ions over the whole molecule. We suggest that RNA conformation plays a role in keeping exon 6B from being spiced into nin-muscle cell mRNA.

Published
1991
Full Text
View/download PDF

45. DNA physical properties determine nucleosome occupancy from yeast to fly

Author

Claude Thermes, Yves d'Aubenton-Carafa, Vincent Miele, Thierry Grange, Cédric Vaillant, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Agence Nationale de la Recherche, ACI, Centre National de la Recherche Scientifique, French Ministère de l'Education et de la Recherche, ANR: 06-PCVI-2006, NT05-1_41977,06-PCVI-2006, NT05-1_41977, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and ANR-06-PCVI-0006,CMIDT,Controlled Membrane Interaction and Destabilisation for DNA Transfer(2006)

Subjects
Models, Molecular, chemistry.chemical_compound, 0302 clinical medicine, Models, Yeasts, MESH: Animals, MESH: Models, Genetic, Promoter Regions, Genetic, Genetics, 0303 health sciences, biology, MESH: Yeasts, MESH: Genomics, MESH: DNA, Genomics, MESH: Saccharomyces cerevisiae, MESH: Gene Expression Regulation, Chromatin, Nucleosomes, DNA-Binding Proteins, MESH: Promoter Regions (Genetics), Histone, Drosophila melanogaster, Fungal, MESH: Nucleic Acid Conformation, Thermodynamics, Promoter Regions (Genetics), MESH: Thermodynamics, MESH: Models, Molecular, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Genes, Fungal, Computational biology, Saccharomyces cerevisiae, DNA-binding protein, MESH: Drosophila melanogaster, 03 medical and health sciences, Genetic, MESH: Nucleosomes, SDV:BBM, Nucleosome, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Models, Genetic, Eukaryotic transcription, Molecular, Promoter, DNA, Linker DNA, chemistry, Gene Expression Regulation, Genes, Nucleic Acid Conformation, biology.protein, MESH: Genes, Fungal, 030217 neurology & neurosurgery, MESH: DNA-Binding Proteins
Abstract

Epigénome er paléogénomie; International audience; Nucleosome positioning plays an essential role in cellular processes by modulating accessibility of DNA to proteins. Here, using only sequence-dependent DNA flexibility and intrinsic curvature, we predict the nucleosome occupancy along the genomes of Saccharomyces cerevisiae and Drosophila melanogaster and demonstrate the predictive power and universality of our model through its correlation with experimentally determined nucleosome occupancy data. In yeast promoter regions, the computed average nucleosome occupancy closely superimposes with experimental data, exhibiting a

Published
2008
Full Text
View/download PDF

46. Prediction of rho-independent Escherichia coli transcription terminators

Author

Yves d'Aubenton Carafa, Edward Brody, and Claude Thermes

Subjects
Genetics, RNA, Biology, Stem-loop, chemistry.chemical_compound, chemistry, Structural Biology, Transcription (biology), Regulatory sequence, Intrinsic termination, Nucleic acid, Nucleic acid structure, Molecular Biology, DNA
Abstract

Escherichia coli rho-independent transcription terminators are characterized by an RNA structure having a G+C-rich stem-loop followed by a series of uridine residues, but they can be only partially predicted by the stability of this structure or by its primary sequence. A large number of such terminators have been identified or proposed in the literature, and we have constituted a list of them (148 found in 1021 x 10(3) base-pairs of E. coli DNA sequences) in order to analyze statistically the corresponding RNA hairpins. We show that the size of the loops presents a narrow distribution, that their sequences are not random, and that most loops are closed by a C.G base-pair. In particular, 55% of the loops are tetranucleotides and the most abundant loop sequences are UUCG and GAAA. These loops are abundant in prokaryotic and eukaryotic RNAs, and are known to enhance the stability of RNA hairpins. We propose that these tetraloops play an important role in the nucleation of the nascent RNA structures, as does also the presence of a C.G base-pair closing a hairpin loop. This analysis allows us to propose a model of formation of an RNA hairpin during the termination process and to construct an algorithm of prediction of the terminators in a given DNA sequence. For the E. coli sequences, it clearly distinguishes inter- from intracistronic terminator-like structures, and selects 141 of the 148 rho-independent terminators given in the literature, with a very low background. It also predicts with reasonable accuracy the in vitro termination efficiency of known rho-independent terminators, as well as predicting the existence of 35 as yet uncharacterized terminators.

Published
1990
Full Text
View/download PDF

47. In vitro splicing of mutually exclusive exons from the chicken beta-tropomyosin gene: role of the branch point location and very long pyrimidine stretch

Author

Domenico Libri, Joëlle Marie, Edward Brody, M Goux-Pelletan, M Y Fiszman, and Yves d'Aubenton-Carafa

Subjects
Transcription, Genetic, RNA Splicing, Molecular Sequence Data, Tropomyosin, Biology, General Biochemistry, Genetics and Molecular Biology, Exon, RNA Precursors, Animals, splice, RNA, Messenger, Cloning, Molecular, Molecular Biology, Genetics, Splice site mutation, Base Sequence, General Immunology and Microbiology, General Neuroscience, Alternative splicing, Nucleic acid sequence, Intron, DNA Restriction Enzymes, Exons, Introns, Kinetics, Pyrimidines, Mutation, RNA splicing, Tandem exon duplication, Chickens, Research Article, HeLa Cells
Abstract

The chicken beta-tropomyosin gene contains 11 exons, two of which are spliced into mRNA only in skeletal muscle. One pair of alternative exons, 6A and 6B, is found in the middle of the gene; they are spliced in a mutually exclusive manner. The non-muscle splice 6A-7 is by far the predominant in vitro reaction in a HeLa cell nuclear extract. A minor product is the 6A-6B splice, which is excluded in all tissues. This minor product results from the use of a branch point located 105 nt upstream of the 3' end of the intron separating exons 6A and 6B. The region between the branch point sequence and the final AG contains a stretch of approximately 80 pyrimidines. We have examined the role of the distance of the branchpoint to the 3' splice site and of the sequences between these two elements. Our results suggest that at least two cis-acting elements contribute to the mutual exclusivity of exons 6A and 6B. The intron between exons 6A and 6B is intrinsically poorly 'spliceable' both because the branch point is too far upstream of the 3' end of the intron to give efficient splicing and because of the particular sequence lying between this branch point and the 3' splice site.

Published
1990
Full Text
View/download PDF

48. DNA Replication Timing Data CorroborateIn SilicoHuman Replication Origin Predictions

Author

Yves d'Aubenton-Carafa, Maxime Huvet, Alain Arneodo, Marie Touchon, Samuel Nicolay, Claude Thermes, and Benjamin Audit

Subjects
DNA Replication, 0303 health sciences, Replication timing, Models, Genetic, Genome, Human, In silico, Timing data, General Physics and Astronomy, Biology, Origin of replication, 01 natural sciences, Pattern Recognition, Automated, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Evolutionary biology, 0103 physical sciences, DNA Replication Timing, Replication (statistics), Animals, Humans, Human genome, 010306 general physics, DNA, 030304 developmental biology
Abstract

We develop a wavelet-based multiscale pattern recognition methodology to disentangle the replication- from the transcription-associated compositional strand asymmetries observed in the human genome. Comparing replication skew profiles to recent high-resolution replication timing data reveals that most of the putative replication origins that border the so-identified replication domains are replicated earlier than their surroundings whereas the central regions replicate late in the S phase. We discuss the implications of this first experimental confirmation of these replication origin predictions that are likely to be early replicating and active in most tissues.

Published
2007
Full Text
View/download PDF

49. Human gene organization driven by the coordination of replication and transcription

Author

Yves d'Aubenton-Carafa, Maxime Huvet, Samuel Nicolay, Alain Arneodo, Benjamin Audit, Marie Touchon, Claude Thermes, Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Génétique des Génomes Bactériens, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
DNA Replication, Letter, Transcription, Genetic, replication origins, Eukaryotic DNA replication, Replication Origin, Computational biology, Biology, Origin of replication, Pre-replication complex, S Phase, 03 medical and health sciences, 0302 clinical medicine, Minichromosome maintenance, Control of chromosome duplication, SeqA protein domain, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene Duplication, Gene Order, Genetics, Humans, genome organization, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Base Sequence, Models, Genetic, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Chromatin, Licensing factor, Genes, Origin recognition complex, DNA, Intergenic, replication domains, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], transcription, 030217 neurology & neurosurgery
Abstract

In this work, we investigated a large-scale organization of the human genes with respect to putative replication origins. We developed an appropriate multiscale method to analyze the nucleotide compositional skew along the genome and found that in more than one-quarter of the genome, the skew profile presents characteristic patterns consisting of successions of N-shaped structures, designated here N-domains, bordered by putative replication origins. Our analysis of recent experimental timing data confirmed that, in a number of cases, domain borders coincide with replication initiation zones active in the early S phase, whereas the central regions replicate in the late S phase. Around the putative origins, genes are abundant and broadly expressed, and their transcription is co-oriented with replication fork progression. These features weaken progressively with the distance from putative replication origins. At the center of domains, genes are rare and expressed in few tissues. We propose that this specific organization could result from the constraints of accommodating the replication and transcription initiation processes at chromatin level, and reducing head-on collisions between the two machineries. Our findings provide a new model of gene organization in the human genome, which integrates transcription, replication, and chromatin structure as coordinated determinants of genome architecture.

Published
2007
Full Text
View/download PDF

50. Analysing grouping of nucleotides in DNA sequences using lumped processes constructed from Markov chains

Author

Yann Guédon, Claude Thermes, Yves d'Aubenton-Carafa, Botanique et Modélisation de l'Architecture des Plantes et des Végétations (UMR AMAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Modeling plant morphogenesis at different scales, from genes to phenotype (VIRTUAL PLANTS), Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de la Recherche Agronomique (INRA)-Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Markov kernel, ADN, Model selection, 01 natural sciences, F30 - Génétique et amélioration des plantes, 010104 statistics & probability, [MATH]Mathematics [math], 3' Untranslated Regions, Mathematics, 0303 health sciences, U10 - Informatique, mathématiques et statistiques, Applied Mathematics, Variable-order Markov model, Agricultural and Biological Sciences (miscellaneous), Markov Chains, Modeling and Simulation, symbols, Markov property, Algorithm, Algorithms, Modèle mathématique, intron, Lumpability, Markov chain, DNA sequence, Markov process, Markov model, 03 medical and health sciences, symbols.namesake, Animals, Humans, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, 0101 mathematics, Technique analytique, 030304 developmental biology, Models, Statistical, Base Sequence, DNA, Sequence Analysis, DNA, L10 - Génétique et amélioration des animaux, Introns, Nucléotide, Examples of Markov chains
Abstract

The most commonly used models for analysing local dependencies in DNA sequences are (high-order) Markov chains. Incorporating knowledge relative to the possible grouping of the nucleotides enables to define dedicated sub-classes of Markov chains. The problem of formulating lumpability hypotheses for a Markov chain is therefore addressed. In the classical approach to lumpability, this problem can be formulated as the determination of an appropriate state space (smaller than the original state space) such that the lumped chain defined on this state space retains the Markov property. We propose a different perspective on lumpability where the state space is fixed and the partitioning of this state space is represented by a one-to-many probabilistic function within a two-level stochastic process. Three nested classes of lumped processes can be defined in this way as sub-classes of first-order Markov chains. These lumped processes enable parsimonious reparameterizations of Markov chains that help to reveal relevant partitions of the state space. Characterizations of the lumped processes on the original transition probability matrix are derived. Different model selection methods relying either on hypothesis testing or on penalized log-likelihood criteria are presented as well as extensions to lumped processes constructed from high-order Markov chains. The relevance of the proposed approach to lumpability is illustrated by the analysis of DNA sequences. In particular, the use of lumped processes enables to highlight differences between intronic sequences and gene untranslated region sequences.

Published
2006
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results