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

Research output: Contribution to journalArticle

586 Citations (Scopus)

Abstract

The mammalian circadian clock involves a transcriptional feedback loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feed back 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.

Original languageEnglish (US)
Pages (from-to)349-354
Number of pages6
JournalScience
Volume338
Issue number6105
DOIs
StatePublished - Oct 19 2012

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Circadian Clocks
RNA Polymerase II
Chromatin
Mammals
Cryptochromes
Genome
Chromatin Assembly and Disassembly
Gene Expression Profiling
Transcriptional Activation
Genes
Transcription Factors
RNA
Messenger RNA
Liver

ASJC Scopus subject areas

  • General

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Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. / Koike, Nobuya; Yoo, Seung Hee; Huang, Hung Chung; Kumar, Vivek; Lee, Choogon; Kim, Tae Kyung; Takahashi, Joseph S.

In: Science, Vol. 338, No. 6105, 19.10.2012, p. 349-354.

Research output: Contribution to journalArticle

Koike, Nobuya ; Yoo, Seung Hee ; Huang, Hung Chung ; Kumar, Vivek ; Lee, Choogon ; Kim, Tae Kyung ; Takahashi, Joseph S. / Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. In: Science. 2012 ; Vol. 338, No. 6105. pp. 349-354.
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