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1. Telomere DNA length regulation is influenced by seasonal temperature differences in short-lived but not in long-lived reef-building corals

Author

Alice Rouan, Melanie Pousse, Nadir Djerbi, Barbara Porro, Guillaume Bourdin, Quentin Carradec, Benjamin CC. Hume, Julie Poulain, Julie Lê-Hoang, Eric Armstrong, Sylvain Agostini, Guillem Salazar, Hans-Joachim Ruscheweyh, Jean-Marc Aury, David A. Paz-García, Ryan McMinds, Marie-Josèphe Giraud-Panis, Romane Deshuraud, Alexandre Ottaviani, Lycia Die Morini, Camille Leone, Lia Wurzer, Jessica Tran, Didier Zoccola, Alexis Pey, Clémentine Moulin, Emilie Boissin, Guillaume Iwankow, Sarah Romac, Colomban de Vargas, Bernard Banaigs, Emmanuel Boss, Chris Bowler, Eric Douville, Michel Flores, Stéphanie Reynaud, Olivier P. Thomas, Romain Troublé, Rebecca Vega Thurber, Serge Planes, Denis Allemand, Stephane Pesant, Pierre E. Galand, Patrick Wincker, Shinichi Sunagawa, Eric Röttinger, Paola Furla, Christian R. Voolstra, Didier Forcioli, Fabien Lombard, and Eric Gilson

Subjects
Science
Abstract

Abstract Telomeres are environment-sensitive regulators of health and aging. Here,we present telomere DNA length analysis of two reef-building coral genera revealing that the long- and short-term water thermal regime is a key driver of between-colony variation across the Pacific Ocean. Notably, there are differences between the two studied genera. The telomere DNA lengths of the short-lived, more stress-sensitive Pocillopora spp. colonies were largely determined by seasonal temperature variation, whereas those of the long-lived, more stress-resistant Porites spp. colonies were insensitive to seasonal patterns, but rather influenced by past thermal anomalies. These results reveal marked differences in telomere DNA length regulation between two evolutionary distant coral genera exhibiting specific life-history traits. We propose that environmentally regulated mechanisms of telomere maintenance are linked to organismal performances, a matter of paramount importance considering the effects of climate change on health.

Published
2023
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2. Tissue-Specific Suppression of Thyroid Hormone Signaling in Various Mouse Models of Aging.

Author

W Edward Visser, Cíntia R Bombardieri, Chantal Zevenbergen, Sander Barnhoorn, Alexandre Ottaviani, Ingrid van der Pluijm, Renata Brandt, Ellen Kaptein, Ramona van Heerebeek, Hans van Toor, George A Garinis, Robin P Peeters, Marco Medici, Willy van Ham, Wilbert P Vermeij, Monique C de Waard, Ronald R de Krijger, Anita Boelen, Joan Kwakkel, John J Kopchick, Edward O List, Joost P M Melis, Veerle M Darras, Martijn E T Dollé, Gijsbertus T J van der Horst, Jan H J Hoeijmakers, and Theo J Visser

Subjects
Medicine, Science
Abstract

DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/-) or intermediate (Ercc1-/Δ-7) progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNA-damaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging.

Published
2016
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3. Acacetin and Chrysin, Two Polyphenolic Compounds, Alleviate Telomeric Position Effect in Human Cells

Author

Amina Boussouar, Caroline Barette, Robert Nadon, Adelaïde Saint-Léger, Natacha Broucqsault, Alexandre Ottaviani, Arva Firozhoussen, Yiming Lu, Laurence Lafanechère, Eric Gilson, Frédérique Magdinier, and Jing Ye

Subjects
DNA damage response, flavanoid, polyphenol, telomere, telomeric position effect, telomere-induced foci, Therapeutics. Pharmacology, RM1-950
Abstract

We took advantage of the ability of human telomeres to silence neighboring genes (telomere position effect or TPE) to design a high-throughput screening assay for drugs altering telomeres. We identified, for the first time, that two dietary flavones, acacetin and chrysin, are able to specifically alleviate TPE in human cells. We further investigated their influence on telomere integrity and showed that both drugs drastically deprotect telomeres against DNA damage response. However, telomere deprotection triggered by shelterin dysfunction does not affect TPE, indicating that acacetin and chrysin target several functions of telomeres. These results show that TPE-based screening assays represent valuable methods to discover new compounds targeting telomeres.

Published
2013
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4. Replication timing of human telomeres is chromosome arm-specific, influenced by subtelomeric structures and connected to nuclear localization.

Author

Nausica Arnoult, Caroline Schluth-Bolard, Anne Letessier, Irena Drascovic, Rachida Bouarich-Bourimi, Judith Campisi, Sahn-Ho Kim, Amina Boussouar, Alexandre Ottaviani, Frédérique Magdinier, Eric Gilson, and Arturo Londoño-Vallejo

Subjects
Genetics, QH426-470
Abstract

The mechanisms governing telomere replication in humans are still poorly understood. To fill this gap, we investigated the timing of replication of single telomeres in human cells. Using in situ hybridization techniques, we have found that specific telomeres have preferential time windows for replication during the S-phase and that these intervals do not depend upon telomere length and are largely conserved between homologous chromosomes and between individuals, even in the presence of large subtelomeric segmental polymorphisms. Importantly, we show that one copy of the 3.3 kb macrosatellite repeat D4Z4, present in the subtelomeric region of the late replicating 4q35 telomere, is sufficient to confer both a more peripheral localization and a later-replicating property to a de novo formed telomere. Also, the presence of beta-satellite repeats next to a newly created telomere is sufficient to delay its replication timing. Remarkably, several native, non-D4Z4-associated, late-replicating telomeres show a preferential localization toward the nuclear periphery, while several early-replicating telomeres are associated with the inner nuclear volume. We propose that, in humans, chromosome arm-specific subtelomeric sequences may influence both the spatial distribution of telomeres in the nucleus and their replication timing.

Published
2010
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5. The D4Z4 macrosatellite repeat acts as a CTCF and A-type lamins-dependent insulator in facio-scapulo-humeral dystrophy.

Author

Alexandre Ottaviani, Sylvie Rival-Gervier, Amina Boussouar, Andrea M Foerster, Delphine Rondier, Sabrina Sacconi, Claude Desnuelle, Eric Gilson, and Frédérique Magdinier

Subjects
Genetics, QH426-470
Abstract

Both genetic and epigenetic alterations contribute to Facio-Scapulo-Humeral Dystrophy (FSHD), which is linked to the shortening of the array of D4Z4 repeats at the 4q35 locus. The consequence of this rearrangement remains enigmatic, but deletion of this 3.3-kb macrosatellite element might affect the expression of the FSHD-associated gene(s) through position effect mechanisms. We investigated this hypothesis by creating a large collection of constructs carrying 1 to >11 D4Z4 repeats integrated into the human genome, either at random sites or proximal to a telomere, mimicking thereby the organization of the 4q35 locus. We show that D4Z4 acts as an insulator that interferes with enhancer-promoter communication and protects transgenes from position effect. This last property depends on both CTCF and A-type Lamins. We further demonstrate that both anti-silencing activity of D4Z4 and CTCF binding are lost upon multimerization of the repeat in cells from FSHD patients compared to control myoblasts from healthy individuals, suggesting that FSHD corresponds to a gain-of-function of CTCF at the residual D4Z4 repeats. We propose that contraction of the D4Z4 array contributes to FSHD physio-pathology by acting as a CTCF-dependent insulator in patients.

Published
2009
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6. From genome wide SNPs to genomic islands of differentiation: the quest for species diagnostic markers in two scleractinian corals,PocilloporaandPorites

Author

Romane Deshuraud, Alexandre Ottaviani, Julie Poulain, Marine Leprêtre, Odette Beluche, Eric Mahieu, Sandrine Lebled, Caroline Belser, Alice Rouan, Clementine Moulin, Emilie Boissin, Guillaume Bourdin, Guillaume Iwankow, Sarah Romac, Sylvain Agostini, Bernard Banaigs, Emmanuel Boss, Chris Bowler, Colomban de Vargas, Eric Douville, Michel Flores, Paola Furla, Pierre Galand, Fabien Lombard, Stéphane Pesant, Stéphanie Reynaud, Matthew B Sullivan, Shinichi Sunagawa, Olivier Thomas, Romain Troublé, Rebecca Vega Thurber, Christian R. Voolstra, Patrick Wincker, Didier Zoccola, Serge Planes, Denis Allemand, Eric Gilson, and Didier Forcioli

Abstract

Coral reefs are of paramount importance in marine ecosystems, where they provide support for a large part of the biodiversity. Being quite sensitive to global changes, they are therefore the prime targets for biodiversity conservation policies. However, such conservation goals require accurate species identification, which are notoriously difficult to get in these highly morphologically variable organisms, rich in cryptic species. There is an acute need for easy-to-use and resolutive species diagnostic molecular markers. The present study builds on the huge sequencing effort developed during the TARA Pacific expedition to develop a genotyping strategy to assign coral samples to the correct species within two coral genera (PoritesandPocillopora). For this purpose, we developed a technique that we called “Divergent Fragment” based on the sequencing of a less than 2kb long diagnostic genomic fragment determined from the metagenomic data of a subset of the corals collected. This method has proven to be rapid, resolvable and cost-effective. Sequencing of PCR fragments nested along the species diagnostic fragment allowed us to assign 232 individuals of the genusPocilloporaand 247 individuals of the genusPoritesto previously identified independent genetic lineages (i.e. species). This genotyping method will allow to fully analyze the coral samples collected across the Pacific during the Tara Pacific expedition and opens technological perspectives in the field of population genomics-guided conservation.

Published
2022
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7. Dynamics and plasticity of chromosome ends: consequences in human pathologies

Author

Frédérique Magdinier, Amina Boussouar, Alexandre Ottaviani, Amadou Bah, Caroline Schluth-Bolard, and Eric Gilson

Subjects
Genetics, Cancer Research, Oncology, Chromosome, Human genome, Hematology, Biology, Subtelomere, Genome, Multiple pathologies, Telomere
Abstract

In eukaryotic cells, chromosome ends of linear chro mosomes are particular regions of the genome formed by telomeres at the very end and subtelomeres, complex sequences that separate telomeres from chromosome-specific r egions. These two regions are highly dynamic are contribute to th e stability and integrity of the human genome. Furt hermore, in human cells, dysregulation of these regions are imp licated in a wide range of physiological events and pathological manifestations. Due to the amount of information av ailable on the biology of telomeres, we will give a n overview and discuss here what is currently known of the regulat ion of telomere length and homeostasis and describe the complex organization of subtelomeric regions and their impl ication in multiple pathologies.

Published
2011
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8. Chromosomal Position Effects and Gene Variegation

Author

Frédérique Magdinier, Alexandre Ottaviani, Eric Gilson, and Caroline Schluth-Bolard

Subjects
Regulation of gene expression, Position effect, Evolutionary biology, Chromosomal Position Effects, Epigenetics, Position-effect variegation, Biology, Gene, Genome, Chromatin
Abstract

One of the most intriguing aspects of epigenetics is the dynamic nature of chromatin and the transmission of various chromatin conformations, sometimes over a large region of the genome. This is likely to involve long-range chromatin interactions, which is well illustrated by the capacity of chromatin to propagate into neighboring loci. Chromatin regulation involves finely tuned processes and it becomes more and more clear that the tri-dimensional organization of genomic domains within the nuclear space also contributes to genome regulation. In eukaryotic genomes, beside non-coding regions, regulatory elements can extend their influence outside of a transcription unit and reside within an independently regulated locus. Thus, sequences with different functions or spatio-temporal activities are juxtaposed next to another. Affecting this equilibrium by changing their relative positioning represents a risk in the maintenance of chromatin architecture, gene regulation and in turn, the fate of a cell. Position effect mechanisms, first discovered and described in model organisms, remain poorly investigated in human pathology. However, common themes are emerging from the review of fundamental research and clinical observations of patients. In this chapter, we try to outline and discuss different examples of diseases linked to position effects and bring into focus potential conserved mechanisms underlying their pathogenesis.

Published
2011
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9. Contributors

Author

Masahiko Abematsu, David W. Anderson, Roberta H. Andronikos, Adriana Arita, Zoya Avramova, Autumn J. Bernal, Javier Campión, Vince Castranova, Frances A. Champagne, Wendy Chao, Fei Chen, Xiaowei Sylvia Chen, Xiaodong Cheng, Lesley Collins, Max Costa, James P. Curley, Walter Doerfler, Tamar Dvash, Thomas Eggermann, Guoping Fan, Tamara B. Franklin, Steffen Gay, Eric Gilson, Johannes Gräff, Hideharu Hashimoto, Naoko Hattori, Zdenko Herceg, Norbert Hochstein, John R. Horton, Simon H. House, Karolina Janitz, Michal Janitz, Randy L. Jirtle, Ji-Hoon E. Joo, Berry Juliandi, Astrid Jungel, Hong Kan, Tae Hoon Kim, Yoon Jung Kim, Hervé Lalucque, Sheila C.S. Lima, Sally A. Litherland, John C. Lucchesi, Hanna Maciejewska-Rodrigues, Frédérique Magdinier, Fabienne Malagnac, Isabelle M. Mansuy, J. Alfredo Martinez, Rahia Mashoodh, Fermin I. Milagro, Ashleigh Miller, Pamela Munster, Susan K. Murphy, Rabih Murr, Kinichi Nakashima, Anja Naumann, Alexandre Ottaviani, Jacob Peedicayil, Gerd P. Pfeifer, Luis Felipe Ribeiro Pinto, Vincenzo Pirrotta, Pier Lorenzo Puri, Tibor A. Rauch, Lee B. Riley, Eric D. Roth, Tania L. Roth, Richard Saffery, Vittorio Sartorelli, Caroline Schluth-Bolard, Barbara Schönfeld, Axel Schumacher, Philippe Silar, Kjetil Søreide, J. David Sweatt, Scott Thomas, Kenneth T. Thurn, Trygve O. Tollefsbol, Toshikazu Ushijima, David A. Wacker, Stefanie Weber, and Xing Zhang

Published
2011
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10. D4Z4 as a prototype of CTCF and lamins-dependent insulator in human cells

Author

Frédérique Magdinier, Alexandre Ottaviani, Caroline Schluth-Bolard, Eric Gilson, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Genetics, Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de biologie et pathologie des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), and Ganivet, Agnès

Subjects
musculoskeletal diseases, CCCTC-Binding Factor, congenital, hereditary, and neonatal diseases and abnormalities, nuclear organization, Recombinant Fusion Proteins, Locus (genetics), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, insulator, Humans, In patient, Enhancer, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Genetics, Cell Nucleus, FSHD, telomere, D4Z4, Extra View, Cell Biology, Position-effect variegation, Subtelomere, Lamin Type A, CTCF, Muscular Dystrophy, Facioscapulohumeral, Telomere, Cell biology, DNA-Binding Proteins, Repressor Proteins, position effect variegation, subtelomere, Insulator Elements, Chromosomes, Human, Pair 4, Protein Multimerization, Lamin, A-type lamins
Abstract

Using cellular models that mimic the organizations of the subtelomeric 4q35 locus found in patients affected with Facio-Scapulo-Humeral Dystrophy (FSHD) and in healthy individuals, we recently investigated the biological function of the D4Z4 macrosatellite in this subtelomeric context.We demonstrated that D4Z4 acts as a CTCF and A-type lamins dependent insulator element exhibiting both enhancer- blocking and barrier activities, and displaces a telomere towards the nuclear periphery. This peripheral positioning activity lies within a short sequence that interacts with CTCF and A-type lamins. Depletion in either of these two proteins suppresses these perinuclear activities, revealing the existence of a subtelomeric sequence that is sufficient to position an adjacent telomere to the nuclear periphery. We discuss here the biological implications of these results in the light of our current knowledge in related fields and the potential implication of other CTCF and A-type lamins insulators in the light of human pathologies.

Published
2010

11. Identification of a perinuclear positioning element in human subtelomeres that requires A-type lamins and CTCF

Author

Frédérique Magdinier, Serge Bauwens, Eric Gilson, Alexandre Ottaviani, Sophie Gazzo, Sylvie Rival-Gervier, Julia Morere, Evelyne Callet-Bauchu, Amina Boussouar, Delphine Rondier, Caroline Schluth-Bolard, Andrea M. Foerster, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), 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), Université de Lyon-Université de Lyon, Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire d'Hématologie, Hospices Civils de Lyon (HCL), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-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)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Magdinier, Frederique

Subjects
CCCTC-Binding Factor, [SDV]Life Sciences [q-bio], Uterine Cervical Neoplasms, Plasma protein binding, Genome, 0302 clinical medicine, Genetics, 0303 health sciences, telomere, General Neuroscience, Subtelomere, Lamin Type A, Female, Insulator Elements, Cell Nucleolus, Protein Binding, congenital, hereditary, and neonatal diseases and abnormalities, Down-Regulation, HUMAIN, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Cell Line, Tumor, Animals, Humans, BIOLOGIE DU DEVELOPPEMENT, [INFO]Computer Science [cs], Molecular Biology, Locus control region, 030304 developmental biology, FSHD, D4Z4, General Immunology and Microbiology, Base Sequence, Carcinoma, genome stability & dynamics, Biological Transport, Epithelial Cells, Locus Control Region, CTCF, Telomere, Repressor Proteins, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Human genome, nuclear periphery, 030217 neurology & neurosurgery, Lamin
Abstract

International audience; The localization of genes within the nuclear space is of paramount importance for proper genome functions. However, very little is known on the cis-acting elements determining subnuclear positioning of chromosome segments. We show here that the D4Z4 human subtelomeric repeat localizes a telomere at the nuclear periphery. This perinuclear activity lies within an 80 bp sequence included within a region known to interact with CTCF and A-type Lamins. We further show that a reduced level of either CTCF or A-type Lamins suppresses the perinuclear activities of D4Z4 and that an array of multimerized D4Z4 sequence, which has lost its ability to bind CTCF and A-type Lamins, is not localized at the periphery. Overall, these findings reveal the existence of an 80 bp D4Z4 sequence that is sufficient to position an adjacent telomere to the nuclear periphery in a CTCF and A-type lamins-dependent manner. Strikingly, this sequence includes a 30 bp GA-rich motif, which binds CTCF and is present at several locations in the human genome.

Published
2009
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12. Polynucléotides isolants issus de l'élément D4Z4 et leurs utilisations dans la transgénèse

Author

Frédérique Magdinier, Eric Gilson, Alexandre Ottaviani, Sylvie Rival-Gervier, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), 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), Université de Lyon-Université de Lyon, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
C12N15/63, C12N15/85, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs]
Abstract

Polynucleotides with insulating properties allowing protection of the expression of a transgene from adjacent cis elements in higher eukaryotic cells. In particular, these polynucleotides can be used for transgenesis, gene therapy and the production of recombinant proteins.; L'invention porte sur des polynucléotides présentant des propriétés isolantes permettant la protection de l'expression d'un transgène à partir d'éléments cis adjacents dans des cellules eucaryotes supérieures. En particulier, ces polynucléotides peuvent être utilisés pour la transgenèse, la thérapie génique et la production de protéines recombinantes.

Published
2009

13. Telomeric position effect: From the yeast paradigm to human pathologies?

Author

Frédérique Magdinier, Alexandre Ottaviani, Eric Gilson, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité mixte de recherche biologie moléculaire de la cellule, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure - Cachan (ENS Cachan), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, and Magdinier, Frederique

Subjects
Aging, Heterochromatin, [SDV]Life Sciences [q-bio], Telomere-Binding Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biochemistry, Histones, 03 medical and health sciences, 0302 clinical medicine, Chromosomal Instability, Yeasts, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene silencing, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epigenetics, Gene Silencing, Cellular Senescence, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, Recombination, Genetic, EPIGENETIC, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genetic Diseases, Inborn, Human diseases, General Medicine, Epigenome, Telomere, Subtelomere, GENOMIQUE, Chromatin, [SDV] Life Sciences [q-bio], Position effect, Eukaryotic Cells, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030217 neurology & neurosurgery
Abstract

International audience; Alteration of the epigenome is associated with a wide range of human diseases. Therefore, deciphering the pathways that regulate the epi-genetic modulation of gene expression is a major milestone for the understanding of diverse biological mechanisms and subsequently human pathologies. Although often evoked, little is known on the implication of telomeric position effect, a silencing mechanism combining telomere architecture and classical heterochromatin features, in human cells. Nevertheless, this particular silencing mechanism has been investigated in different organisms and several ingredients are likely conserved during evolution. Subtelomeres are highly dynamic regions near the end of the chromosomes that are prone to recombination and may buffer or facilitate the spreading of silencing that emanates from the telomere. Therefore, the composition and integrity of these regions also concur to the propensity of telomeres to regulate the expression, replication and recombi-nation of adjacent regions. Here we describe the similarities and disparities that exist among the different species at chromosome ends with regard to telomeric silencing regulation with a special accent on its implication in numerous human pathologies.

Published
2008
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14. Interactions of cryptolepine and neocryptolepine with unusual DNS structures

Author

Edwin De Pauw, Jean-Louis Mergny, Sabine Van Miert, Luc Pieters, Frédéric Rosu, Emilie Thetiot, Patrizia Alberti, Valérie Gabelica, Jean-François Riou, Alexandre Ottaviani, and Lionel Guittat

Subjects
Indoles, Stereochemistry, Cryptolepis sanguinolenta, Biochemistry, Mass Spectrometry, Indole Alkaloids, Substrate Specificity, Structure-Activity Relationship, chemistry.chemical_compound, Alkaloids, Biological property, Animals, heterocyclic compounds, A-DNA, Enzyme Inhibitors, Telomerase, biology, Cryptolepis, DNA, General Medicine, biology.organism_classification, Neocryptolepine, Cryptolepine, chemistry, Duplex (building), Quinolines, Nucleic Acid Conformation, Protein Binding
Abstract

Cryptolepine, the main alkaloid present in the roots of Cryptolepis sanguinolenta, presents a large spectrum of biological properties. It has been reported to behave like a DNA intercalator with a preference for GC-rich sequences. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of cryptolepine and neocryptolepine for DNA structures among duplexes, triplexes, quadruplexes and single strands. Our data confirm that cryptolepine and neocryptolepine prefer GC over AT-rich duplex sequences, but also recognize triplex and quadruplex structures. These compounds are weak telomerase inhibitors and exhibit a significant preference for triplexes over quadruplexes or duplexes.

Published
2003

16. Polynucléotides insulateurs dérivés de l'élément D4Z4 et leurs utilisations dans la transgénèse

Author

Frédérique Magdinier, Eric Gilson, Alexandre Ottaviani, Sylvie Rival-Gervier, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), 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), Université de Lyon-Université de Lyon, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
C12N15/12, C12N15/63, C12N15/85, C12N5/10, C12N5/08, A61K48/00, A61P35/00, A61P29/00, A61P37/00, C12P21/00, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs]
Abstract

Polynucléotides possédant des propriétés insulatrices permettant de protéger en cis l'expression d'un transgène des éléments adjacents dans les cellules d'eucaryotes supérieurs. Ces polynucléotides peuvent notamment être utilisés pour la transgénèse, la thérapie génique et la production de protéines recombinantes.

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