Molecular components of the circadian clock in mammals

Research output: Contribution to journalReview articlepeer-review

163 Scopus citations


The circadian clock mechanism in animals involves a transcriptional feedback loop in which the bHLH-PAS proteins CLOCK and BMAL1 form a transcriptional activator complex to activate the transcription of the Period and Cryptochrome genes, which in turn feed back to repress their own transcription. In the mouse liver, CLOCK and BMAL1 interact with the regulatory regions of thousands of genes, which are both cyclically and constitutively expressed. The circadian transcription in the liver is clustered in phase and this is accompanied by circadian occupancy of RNA polymerase II recruitment and initiation. These changes also lead to circadian fluctuations in histone H3 lysine4 trimethylation (H3K4me3) as well as H3 lysine9 acetylation (H3K9ac) and H3 lysine27 acetylation (H3K27ac). Thus, the circadian clock regulates global transcriptional poise and chromatin state by regulation of RNA polymerase II.

Original languageEnglish (US)
Pages (from-to)6-11
Number of pages6
JournalDiabetes, Obesity and Metabolism
Issue numberS1
StatePublished - Sep 1 2015


  • ChIP-seq
  • Chromatin
  • Circadian clock
  • Clock gene
  • Epigenetics
  • Histone modifications
  • RNA polymerase II
  • RNA-seq
  • Transcription

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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