Transcriptional regulatory logic of the diurnal cycle in the mouse liver.
Details
Serval ID
serval:BIB_9EE2433B0953
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transcriptional regulatory logic of the diurnal cycle in the mouse liver.
Journal
PLoS biology
Working group(s)
CycliX consortium
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
15
Number
4
Pages
e2001069
Language
english
Abstract
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.
Keywords
ARNTL Transcription Factors/genetics, ARNTL Transcription Factors/metabolism, Animals, CLOCK Proteins/genetics, CLOCK Proteins/metabolism, Chromatin Immunoprecipitation, Circadian Clocks/genetics, Circadian Rhythm/genetics, Deoxyribonuclease I/genetics, Deoxyribonuclease I/metabolism, Fasting, Gene Expression Regulation, Liver/physiology, Male, Mice, Inbred C57BL, Mice, Knockout, Multiprotein Complexes/metabolism, Promoter Regions, Genetic, RNA Polymerase II/genetics, Transcription Factors/genetics, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
29/04/2017 16:36
Last modification date
18/10/2023 6:10