Transcriptional regulatory logic of the diurnal cycle in the mouse liver
| العنوان: | Transcriptional regulatory logic of the diurnal cycle in the mouse liver |
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| المؤلفون: | Irina Krier, Donatella Canella, Felix Naef, Sunil K. Raghav, Nouria Hernandez, Benjamin D. Weger, Alexandra Styliani Kalantzi, Teemu Andersin, Guillaume Rey, Matteo Dal Peraro, Frédéric Gachon, Ueli Schibler, Federica Gilardi, Jonathan Sobel, Bart Deplancke |
| المساهمون: | CycliX consortium |
| المصدر: | PLoS Biology PLoS biology, vol. 15, no. 4, pp. e2001069 PLoS Biology, Vol 15, Iss 4, p e2001069 (2017) |
| بيانات النشر: | Public Library of Science (PLoS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Transcription, Genetic, Hydrolases, Circadian clock, CLOCK Proteins, Gene Expression, Genetic Footprinting, RNA polymerase II, Biochemistry, Cell Signaling, Diurnal cycle, Transcription (biology), Gene expression, Transcriptional regulation, Biology (General), Promoter Regions, Genetic, Genetics, Mice, Knockout, Deoxyribonucleases, biology, ARNTL Transcription Factors, General Neuroscience, Fasting, Circadian Rhythm, Enzymes, Cell biology, Circadian Rhythms, Circadian Oscillators, Histone, DNA footprinting, Liver, Genetic Oscillators, RNA Polymerase II, General Agricultural and Biological Sciences, Genomic Signal Processing, Research Article, Signal Transduction, Chromatin Immunoprecipitation, QH301-705.5, Nucleases, Genetic Fingerprinting and Footprinting, Research and Analysis Methods, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rhythm, ARNTL Transcription Factors/genetics, ARNTL Transcription Factors/metabolism, Animals, CLOCK Proteins/genetics, CLOCK Proteins/metabolism, Circadian Clocks/genetics, Circadian Rhythm/genetics, Deoxyribonuclease I/genetics, Deoxyribonuclease I/metabolism, Gene Expression Regulation, Liver/physiology, Mice, Inbred C57BL, Multiprotein Complexes/metabolism, RNA Polymerase II/genetics, Transcription Factors/genetics, Circadian Clocks, DNA-binding proteins, Deoxyribonuclease I, Gene Regulation, Molecular Biology Techniques, Molecular Biology, Transcription factor, Biology and life sciences, General Immunology and Microbiology, Proteins, Cell Biology, Regulatory Proteins, 030104 developmental biology, Multiprotein Complexes, Enzymology, biology.protein, Chronobiology, Chromatin immunoprecipitation, Transcription Factors |
| الوصف: | Many organisms exhibit temporal rhythms in gene expression that propel diurnal cycles in physiology. In the liver of mammals, these rhythms are controlled by transcription–translation feedback loops of the core circadian clock and by feeding–fasting cycles. To better understand the regulatory interplay between the circadian clock and feeding rhythms, we mapped DNase I hypersensitive sites (DHSs) in the mouse liver during a diurnal cycle. The intensity of DNase I cleavages cycled at a substantial fraction of all DHSs, suggesting that DHSs harbor regulatory elements that control rhythmic transcription. Using chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq), we found that hypersensitivity cycled in phase with RNA polymerase II (Pol II) loading and H3K27ac histone marks. We then combined the DHSs with temporal Pol II profiles in wild-type (WT) and Bmal1-/- livers to computationally identify transcription factors through which the core clock and feeding–fasting cycles control diurnal rhythms in transcription. While a similar number of mRNAs accumulated rhythmically in Bmal1-/- compared to WT livers, the amplitudes in Bmal1-/- were generally lower. The residual rhythms in Bmal1-/- reflected transcriptional regulators mediating feeding–fasting responses as well as responses to rhythmic systemic signals. Finally, the analysis of DNase I cuts at nucleotide resolution showed dynamically changing footprints consistent with dynamic binding of CLOCK:BMAL1 complexes. Structural modeling suggested that these footprints are driven by a transient heterotetramer binding configuration at peak activity. Together, our temporal DNase I mappings allowed us to decipher the global regulation of diurnal transcription rhythms in the mouse liver. Author summary The molecular circadian clock is conserved from cyanobacteria to mammals and is believed to align behavioral and biochemical processes with the day’s 24-h diurnal cycle. How the circadian clock and feeding rhythm transcriptionally interact and what the contribution is of cis-regulatory modules to this interconnection has not yet been fully elucidated. To address these questions, we explored the dynamics of accessible regions, histone modifications, and RNA polymerase II loading on the scale of hours in the liver of wild-type (normal) mice and mice that are mutant for the clock master regulator BMAL1. This allowed us to uncover circadian clock–and feeding-dependent gene regulatory networks. Furthermore, we dissected the chromatin accessibility around BMAL1-binding sites at base pair resolution. This enabled us to develop a new DNA-binding model for BMAL1/CLOCK involving the formation of a heterotetramer configuration at times of peak activity. Overall, these temporal profiles provide insight into the global regulation of daily transcription rhythms in the mouse liver. |
| وصف الملف: | application/pdf |
| تدمد: | 1545-7885 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfc5af09af63222c47c01043b35827bf https://doi.org/10.1371/journal.pbio.2001069 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bfc5af09af63222c47c01043b35827bf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15457885 |
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