6 results on '"Cajan, J."'
Search Results
2. Differential regulation of RNA polymerase III genes during liver regeneration
- Author
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Meghdad Yeganeh, Cristian Carmeli, Dominic Villeneuve, Mauro Delorenzi, Winship Herr, Leonor Rib, Nouria Hernandez, Viviane Praz, Nicolas Guex, CycliX consortium, Hernandez, N., Delorenzi, M., Deplancke, B., Desvergne, B., Guex, N., Herr, W., Naef, F., Rougemont, J., Schibler, U., Andersin, T., Cousin, P., Gilardi, F., Gos, P., Lammers, F., Lopes, M., Mange, F., Minocha, S., Raghav, S., Villeneuve, D., Fabbretti, R., Vlegel, V., Xenarios, I., Migliavacca, E., Praz, V., David, F., Jarosz, Y., Kuznetsov, D., Liechti, R., Martin, O., Delafontaine, J., Cajan, J., Carmeli, C., Gustafson, K., Krier, I., Leleu, M., Molina, N., Naldi, A., Rib, L., Sobel, J., Symul, L., Bounova, G., and Jacquet, P.
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Chromatin Immunoprecipitation ,Transcription, Genetic ,DNA polymerase ,DNA polymerase II ,viruses ,RNA polymerase II ,RNA polymerase III ,Histones ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Transcription (biology) ,Genetics ,Animals ,Hepatectomy ,Humans ,Gene ,030304 developmental biology ,0303 health sciences ,biology ,Cell Cycle ,Gene regulation, Chromatin and Epigenetics ,Gene Expression Regulation, Developmental ,RNA Polymerase III ,Histone-Lysine N-Methyltransferase ,Liver regeneration ,Liver Regeneration ,Housekeeping gene ,Cell biology ,Liver ,biology.protein ,RNA Polymerase II ,Cell Division ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Mouse liver regeneration after partial hepatectomy involves cells in the remaining tissue synchronously entering the cell division cycle. We have used this system and H3K4me3, Pol II and Pol III profiling to characterize adaptations in Pol III transcription. Our results broadly define a class of genes close to H3K4me3 and Pol II peaks, whose Pol III occupancy is high and stable, and another class, distant from Pol II peaks, whose Pol III occupancy strongly increases after partial hepatectomy. Pol III regulation in the liver thus entails both highly expressed housekeeping genes and genes whose expression can adapt to increased demand.
- Published
- 2019
3. A multiplicity of factors contributes to selective RNA polymerase III occupancy of a subset of RNA polymerase III genes in mouse liver
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Mauro Delorenzi, Irina Krier, Teemu Andersin, Li Long, Nicolas Guex, Arnaud Fortier, David Bernasconi, Marion Leleu, Guillaume Rey, Julia Cajan, Fabrice P. A. David, Winship Herr, Fabienne Lammers, Sunil K. Raghav, Olivier Martin, Jacques Rougemont, Aurélien Naldi, Roberto Fabbretti, Eugenia Migliavacca, Pascal Gos, Viviane Praz, Robin Liechti, Ueli Schibler, Gwendal LeMartelot, Nouria Hernandez, Laura Symul, Pascal Cousin, Frederick J. Ross, Yohan Jarosz, Béatrice Desvergne, Donatella Canella, Nacho Molina, Ioannis Xenarios, Felix Naef, Lucas Sinclair, Volker Vlegel, Federica Gilardi, Gwendal Le Martelot, Bart Deplancke, Dmitry Kuznetsov, University of Zurich, Delorenzi, Mauro, CycliX Consortium, Hernandez, N., Delorenzi, M., Deplancke, B., Desvergne, B., Guex, N., Herr, W., Naef, F., Rougemont, J., Schibler, U., Andersin, T., Cousin, P., Gilardi, F., Gos, P., Le Martelot, G., Lammers, F., Canella, D., Raghav, S., Fabbretti, R., Fortier, A., Long, L., Vlegel, V., Xenarios, I., Migliavacca, E., Praz, V., David, F., Jarosz, Y., Kuznetsov, D., Liechti, R., Martin, O., Ross, F., Sinclair, L., Cajan, J., Krier, I., Leleu, M., Molina, N., Naldi, A., Rey, G., Symul, L., and Bernasconi, D.
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Male ,Chromatin Immunoprecipitation ,2716 Genetics (clinical) ,Pseudogene ,genetic processes ,Biology ,RNA polymerase III ,Mice ,chemistry.chemical_compound ,RNA, Transfer ,SX00 SystemsX.ch ,1311 Genetics ,Transcription (biology) ,RNA polymerase ,Gene expression ,Genetics ,Animals ,Humans ,SX04 CycliX ,Gene ,Genetics (clinical) ,Oligonucleotide Array Sequence Analysis ,Models, Genetic ,Gene Expression Profiling ,Research ,RNA Polymerase III ,RNA ,Genomics ,Sequence Analysis, DNA ,Molecular biology ,Mice, Inbred C57BL ,enzymes and coenzymes (carbohydrates) ,Liver ,chemistry ,Transfer RNA ,570 Life sciences ,biology ,bacteria ,Chromatin Immunoprecipitation/methods ,Genomics/methods ,Liver/metabolism ,RNA Polymerase III/genetics ,RNA Polymerase III/metabolism ,RNA, Transfer/genetics ,RNA, Transfer/metabolism ,Sequence Analysis, DNA/methods - Abstract
The genomic loci occupied by RNA polymerase (RNAP) III have been characterized in human culture cells by genome-wide chromatin immunoprecipitations, followed by deep sequencing (ChIP-seq). These studies have shown that only ∼40% of the annotated 622 human tRNA genes and pseudogenes are occupied by RNAP-III, and that these genes are often in open chromatin regions rich in active RNAP-II transcription units. We have used ChIP-seq to characterize RNAP-III-occupied loci in a differentiated tissue, the mouse liver. Our studies define the mouse liver RNAP-III-occupied loci including a conserved mammalian interspersed repeat (MIR) as a potential regulator of an RNAP-III subunit-encoding gene. They reveal that synteny relationships can be established between a number of human and mouse RNAP-III genes, and that the expression levels of these genes are significantly linked. They establish that variations within the A and B promoter boxes, as well as the strength of the terminator sequence, can strongly affect RNAP-III occupancy of tRNA genes. They reveal correlations with various genomic features that explain the observed variation of 81% of tRNA scores. In mouse liver, loci represented in the NCBI37/mm9 genome assembly that are clearly occupied by RNAP-III comprise 50 Rn5s (5S RNA) genes, 14 known non-tRNA RNAP-III genes, nine Rn4.5s (4.5S RNA) genes, and 29 SINEs. Moreover, out of the 433 annotated tRNA genes, half are occupied by RNAP-III. Transfer RNA gene expression levels reflect both an underlying genomic organization conserved in dividing human culture cells and resting mouse liver cells, and the particular promoter and terminator strengths of individual genes.
- Published
- 2012
4. Quantifying ChIP-seq data: a spiking method providing an internal reference for sample-to-sample normalization
- Author
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Bonhoure, Nicolas, Bounova, Gergana, Bernasconi, David, Praz, Viviane, Lammers, Fabienne, Canella, Donatella, Willis, Ian M., Herr, Winship, Hernandez, Nouria, Delorenzi, Mauro, Deplancke, Bart, Desvergne, Béatrice, Guex, Nicolas, Naef, Felix, Rougemont, Jacques, Schibler, Ueli, Andersin, Teemu, Cousin, Pascal, Gilardi, Federica, Gos, Pascal, Raghav, Sunil, Villeneuve, Dominic, Fabbretti, Roberto, Vlegel, Volker, Xenarios, Ioannis, Migliavacca, Eugenia, David, Fabrice, Jarosz, Yohan, Kuznetsov, Dmitry, Liechti, Robin, Martin, Olivier, Delafontaine, Julien, Cajan, Julia, Gustafson, Kyle, Krier, Irina, Leleu, Marion, Molina, Nacho, Naldi, Aurélien, Rib, Leonor, Symul, Laura, CycliX Consortium, Hernandez, N., Delorenzi, M., Deplancke, B., Desvergne, B., Guex, N., Herr, W., Naef, F., Rougemont, J., Schibler, U., Andersin, T., Cousin, P., Gilardi, F., Gos, P., Lammers, F., Raghav, S., Villeneuve, D., Fabbretti, R., Vlegel, V., Xenarios, I., Migliavacca, E., Praz, V., David, F., Jarosz, Y., Kuznetsov, D., Liechti, R., Martin, O., Delafontaine, J., Cajan, J., Gustafson, K., Krier, I., Leleu, M., Molina, N., Naldi, A., Rib, L., Symul, L., Bounova, G., University of Zurich, and Hernandez, N
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Quality Control ,Normalization (statistics) ,2716 Genetics (clinical) ,Chromatin Immunoprecipitation ,Occupancy ,SX20 Research, Technology and Development Projects ,Immunoprecipitation ,Sample (material) ,Method ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,SX00 SystemsX.ch ,1311 Genetics ,Genetics ,Animals ,Humans ,Genetics(clinical) ,SX04 CycliX ,Genetics (clinical) ,030304 developmental biology ,Quantile normalization ,0303 health sciences ,Computational Biology ,High-Throughput Nucleotide Sequencing ,Reproducibility of Results ,Reference Standards ,Chromatin ,570 Life sciences ,biology ,Spike (software development) ,Biological system ,Chromatin immunoprecipitation ,030217 neurology & neurosurgery - Abstract
Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments are widely used to determine, within entire genomes, the occupancy sites of any protein of interest, including, for example, transcription factors, RNA polymerases, or histones with or without various modifications. In addition to allowing the determination of occupancy sites within one cell type and under one condition, this method allows, in principle, the establishment and comparison of occupancy maps in various cell types, tissues, and conditions. Such comparisons require, however, that samples be normalized. Widely used normalization methods that include a quantile normalization step perform well when factor occupancy varies at a subset of sites, but may miss uniform genome-wide increases or decreases in site occupancy. We describe a spike adjustment procedure (SAP) that, unlike commonly used normalization methods intervening at the analysis stage, entails an experimental step prior to immunoprecipitation. A constant, low amount from a single batch of chromatin of a foreign genome is added to the experimental chromatin. This “spike” chromatin then serves as an internal control to which the experimental signals can be adjusted. We show that the method improves similarity between replicates and reveals biological differences including global and largely uniform changes.
- Published
- 2014
5. Rhythmic Changes in Gene Activation Power the Circadian Clock
- Author
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Gwendal Le Martelot, Donatella Canella, Laura Symul, Eugenia Migliavacca, Federica Gilardi, Robin Liechti, Olivier Martin, Keith Harshman, Mauro Delorenzi, Béatrice Desvergne, Winship Herr, Bart Deplancke, Ueli Schibler, Jacques Rougemont, Nicolas Guex, Nouria Hernandez, Felix Naef, CycliX Consortium, University of Zurich, Hernandez, Nouria, CycliX Consortium, Hernandez, N., Delorenzi, M., Deplancke, B., Desvergne, B., Guex, N., Herr, W., Naef, F., Rougemont, J., Schibler, U., Andersin, T., Cousin, P., Gilardi, F., Gos, P., Le Martelot, G., Lammers, F., Canella, D., Raghav, S., Fabbretti, R., Fortier, A., Long, L., Vlegel, V., Xenarios, I., Migliavacca, E., Praz, V., David, F., Jarosz, Y., Kuznetsov, D., Liechti, R., Martin, O., Delafontaine, J., Sinclair, L., Cajan, J., Krier, I., Leleu, M., Molina, N., Naldi, A., Rey, G., Symul, L., and Bernasconi, D.
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Male ,Time Factors ,Transcription, Genetic ,Circadian clock ,RNA polymerase II ,Biochemistry ,Epigenesis, Genetic ,Histones ,Mice ,0302 clinical medicine ,SX00 SystemsX.ch ,Transcription (biology) ,2400 General Immunology and Microbiology ,Gene expression ,Molecular Cell Biology ,Transcriptional regulation ,RNA Processing, Post-Transcriptional ,Biology (General) ,Promoter Regions, Genetic ,Regulation of gene expression ,Genetics ,0303 health sciences ,Reverse Transcriptase Polymerase Chain Reaction ,General Neuroscience ,Systems Biology ,2800 General Neuroscience ,Genomics ,Chromatin ,Circadian Rhythm ,Liver ,DNA methylation ,Synopsis ,RNA Polymerase II ,Transcription Initiation Site ,General Agricultural and Biological Sciences ,Half-Life ,Research Article ,Chromatin Immunoprecipitation ,SX20 Research, Technology and Development Projects ,QH301-705.5 ,E-box ,1100 General Agricultural and Biological Sciences ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Rhythm ,1300 General Biochemistry, Genetics and Molecular Biology ,Animals ,Circadian rhythm ,RNA, Messenger ,SX04 CycliX ,Gene ,Post-transcriptional regulation ,030304 developmental biology ,Chromatin Assembly and Disassembly ,DNA Methylation ,Histones/genetics ,Histones/metabolism ,Kinetics ,Liver/cytology ,Liver/metabolism ,Mice, Inbred C57BL ,Models, Genetic ,RNA Polymerase II/genetics ,RNA Polymerase II/metabolism ,RNA, Messenger/analysis ,RNA, Messenger/metabolism ,Transcriptome ,General Immunology and Microbiology ,Computational Biology ,Promoter ,biology.protein ,570 Life sciences ,biology ,Chromatin immunoprecipitation ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Genome-wide rhythms in RNA polymerase II loading and dynamic chromatin remodeling underlie periodic gene expression during diurnal cycles in the mouse liver., Interactions of cell-autonomous circadian oscillators with diurnal cycles govern the temporal compartmentalization of cell physiology in mammals. To understand the transcriptional and epigenetic basis of diurnal rhythms in mouse liver genome-wide, we generated temporal DNA occupancy profiles by RNA polymerase II (Pol II) as well as profiles of the histone modifications H3K4me3 and H3K36me3. We used these data to quantify the relationships of phases and amplitudes between different marks. We found that rhythmic Pol II recruitment at promoters rather than rhythmic transition from paused to productive elongation underlies diurnal gene transcription, a conclusion further supported by modeling. Moreover, Pol II occupancy preceded mRNA accumulation by 3 hours, consistent with mRNA half-lives. Both methylation marks showed that the epigenetic landscape is highly dynamic and globally remodeled during the 24-hour cycle. While promoters of transcribed genes had tri-methylated H3K4 even at their trough activity times, tri-methylation levels reached their peak, on average, 1 hour after Pol II. Meanwhile, rhythms in tri-methylation of H3K36 lagged transcription by 3 hours. Finally, modeling profiles of Pol II occupancy and mRNA accumulation identified three classes of genes: one showing rhythmicity both in transcriptional and mRNA accumulation, a second class with rhythmic transcription but flat mRNA levels, and a third with constant transcription but rhythmic mRNAs. The latter class emphasizes widespread temporally gated posttranscriptional regulation in the mouse liver., Author Summary In mammalian organs such as the liver, many metabolic and physiological processes occur preferentially at specific times during the 24-hour daily cycle. The timing of these rhythmic functions depends on a complex interplay between the endogenous circadian clock and environmental timing cues relayed through the master circadian clock in the suprachiasmatic nucleus, or via feeding rhythms. These rhythms can be implemented on several regulatory levels, and here we aimed at a better understanding of the transcriptional and epigenetic changes that regulate diurnal rhythms. We performed genome-wide analysis of the locations of RNA polymerase II (Pol II) and the epigenetic histone modifications H3K4me3 and H3K36me3 at specific times of day, relating these data to mRNA expression levels. Our analyses show that Pol II transcriptional rhythms are biphasic in mouse liver, having predominant peak activities in the morning and evening. Moreover, dynamic changes in histone marks lag transcription rhythms genome-wide, indicating that the epigenetic landscape can be remodeled during the 24-hour cycle. Finally, a quantitative analysis of temporal Pol II and mRNA accumulation profiles indicates that posttranscriptional regulation significantly contributes to the amplitude and phase of mRNA accumulation profiles. While many studies have analyzed how transcription and chromatin states are modified during irreversible cell differentiation processes, our work highlights how these states can evolve reversibly in a system exhibiting periodicity in time.
- Published
- 2012
6. Genome-Wide Analysis of SREBP1 Activity around the Clock Reveals Its Combined Dependency on Nutrient and Circadian Signals
- Author
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Felix Naef, Bart Deplancke, Laura Symul, Dmitry Kuznetsov, Aurélien Naldi, Winship Herr, Ioannis Xenarios, Nouria Hernandez, Federica Gilardi, Nicolas GUEX, Beatrice Desvergne, Guillaume Rey, CycliX Consortium, Hernandez, N., Delorenzi, M., Deplancke, B., Desvergne, B., Guex, N., Herr, W., Naef, F., Rougemont, J., Schibler, U., Andersin, T., Cousin, P., Gilardi, F., Gos, P., Martelot, G., Lammers, F., Canella, D., Raghav, S., Fabbretti, R., Fortier, A., Long, L., Vlegel, V., Xenarios, I., Migliavacca, E., Praz, V., David, F., Jarosz, Y., Kuznetsov, D., Liechti, R., Martin, O., Delafontaine, J., Sinclair, L., Cajan, J., Krier, I., Leleu, M., Molina, N., Naldi, A., Rey, G., Symul, L., Bernasconi, D., Baruchet, M., University of Zurich, and Guex, Nicolas
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2716 Genetics (clinical) ,Cancer Research ,lcsh:QH426-470 ,SX20 Research, Technology and Development Projects ,Circadian clock ,CLOCK Proteins ,Biology ,Mice ,SX00 SystemsX.ch ,1311 Genetics ,Circadian Clocks ,1312 Molecular Biology ,Genetics ,Transcriptional regulation ,Animals ,Homeostasis ,1306 Cancer Research ,Circadian rhythm ,SX04 CycliX ,Molecular Biology ,Transcription factor ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,Regulation of gene expression ,Binding Sites ,Genome ,Lipid Metabolism ,Bacterial circadian rhythms ,Circadian Rhythm ,Sterol regulatory element-binding protein ,Cell biology ,lcsh:Genetics ,1105 Ecology, Evolution, Behavior and Systematics ,Gene Expression Regulation ,Hepatocyte Nuclear Factor 4 ,570 Life sciences ,biology ,Sterol Regulatory Element Binding Protein 1 ,Protein Binding ,Research Article - Abstract
In mammals, the circadian clock allows them to anticipate and adapt physiology around the 24 hours. Conversely, metabolism and food consumption regulate the internal clock, pointing the existence of an intricate relationship between nutrient state and circadian homeostasis that is far from being understood. The Sterol Regulatory Element Binding Protein 1 (SREBP1) is a key regulator of lipid homeostasis. Hepatic SREBP1 function is influenced by the nutrient-response cycle, but also by the circadian machinery. To systematically understand how the interplay of circadian clock and nutrient-driven rhythm regulates SREBP1 activity, we evaluated the genome-wide binding of SREBP1 to its targets throughout the day in C57BL/6 mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding pattern. In particular, different expression phases were observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. Binding sites for Hepatocyte Nuclear Factor 4 (HNF4) were specifically enriched in the close proximity of SREBP1 peaks of genes, whose expression was shifted by about 8 hours with respect to SREBP1 binding. Thus, the cross-talk between hepatic HNF4 and SREBP1 may underlie the expression timing of this subgroup of SREBP1 targets. Interestingly, the proper temporal expression profile of these genes was dramatically changed in Bmal1 −/− mice upon time-restricted feeding, for which a rhythmic, but slightly delayed, binding of SREBP1 was maintained. Collectively, our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity, strongly dependent from the circadian clock, exists. This system allows us to fine tune the expression timing of SREBP1 target genes, thus helping to temporally separate the different physiological processes in which these genes are involved., Author Summary Circadian rhythmicity is part of our innate behavior and controls many physiological processes, such as sleeping and waking, activity, neurotransmitter production and a number of metabolic pathways. In mammals, the central circadian pacemaker in the hypothalamus is entrained on a daily basis by environmental cues (i.e. light), thus setting the period length and synchronizing the rhythms of all cells in the body. In the last decades, numerous investigations have highlighted the importance of the internal timekeeping mechanism for maintenance of organism health and longevity. Indeed, the reciprocal regulation of circadian clock and metabolism is now commonly accepted, although still poorly understood at the molecular level. Our global analysis of DNA binding along the day of Sterol Regulatory Element Binding Protein 1 (SREBP1), a key regulator of lipid biosynthesis, represents the first tool to comprehensively explore how its activity is connected to circadian-driven regulatory events. We show that the regulation of SREBP1 action by nutrients relies mainly on the control of its subcellular localization, while the circadian clock influences the promoter specific activity of SREBP1 within the nucleus. Furthermore, we identify the Hepatocyte Nuclear Factor 4 (HNF4) as a putative player in the cross-talk between molecular clock and metabolic regulation.
- Published
- 2014
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