Transcriptional Architecture and Chromatin Landscape of the Core Circadian Clock in Mammals
Nobuya Koike,Seung Hee Yoo,Hung Chung Huang,Vivek Kumar,Choogon Lee,Tae Kyung Kim,Joseph S. Takahashi +6 more
TLDR
The transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver is interrogated and a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II recruitment, RNA expression, and chromatin states is found.Abstract:
The mammalian circadian clock involves a transcriptional feed back loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression, and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases: a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Only 22% of messenger RNA (mRNA) cycling genes are driven by de novo transcription, suggesting that both transcriptional and posttranscriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.read more
Citations
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Journal ArticleDOI
A circadian gene expression atlas in mammals: Implications for biology and medicine
TL;DR: High-resolution multiorgan expression data is generated showing that nearly half of all genes in the mouse genome oscillate with circadian rhythm somewhere in the body, and the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes.
Journal ArticleDOI
Transcriptional architecture of the mammalian circadian clock
TL;DR: Genome-wide analyses of the clock transcriptional feedback loop have revealed a global circadian regulation of processes such as transcription factor occupancy, RNA polymerase II recruitment and initiation, nascent transcription, and chromatin remodelling.
Journal ArticleDOI
Post-transcriptional gene regulation by mRNA modifications
TL;DR: N6-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses.
Journal ArticleDOI
Molecular architecture of the mammalian circadian clock.
TL;DR: Recent advances in understanding of the core molecular clock are highlighted and how it utilizes diverse transcriptional and post-transcriptional mechanisms to impart temporal control onto mammalian physiology is highlighted.
Book ChapterDOI
Molecular components of the Mammalian circadian clock
TL;DR: This work has shown that there are other molecular circadian oscillators which can act independently of the transcription-based clock in all species which have been tested.
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