Transcriptional regulatory logic of the diurnal cycle in the mouse liver
| Autor: | 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 |
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| Přispěvatelé: | CycliX consortium |
| Rok vydání: | 2017 |
| Předmět: |
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 |
| Zdroj: | PLoS Biology PLoS biology, vol. 15, no. 4, pp. e2001069 PLoS Biology, Vol 15, Iss 4, p e2001069 (2017) |
| ISSN: | 1545-7885 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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