Transcriptional architecture and chromatin landscape of the core circadian clock in mammals

Science. 2012 Oct 19;338(6105):349-54. doi: 10.1126/science.1226339. Epub 2012 Aug 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / metabolism
  • Animals
  • CLOCK Proteins / metabolism
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly / genetics
  • Circadian Clocks / genetics*
  • Cryptochromes / genetics*
  • DNA, Intergenic
  • Enhancer Elements, Genetic
  • Epigenesis, Genetic*
  • Gene Expression Profiling
  • Genetic Loci
  • Histones / metabolism
  • Liver / metabolism
  • Liver / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Period Circadian Proteins / genetics
  • RNA Polymerase II / metabolism
  • RNA, Messenger / genetics
  • Transcription, Genetic*
  • Transcriptional Activation*


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Chromatin
  • Cryptochromes
  • DNA, Intergenic
  • Histones
  • Per2 protein, mouse
  • Period Circadian Proteins
  • RNA, Messenger
  • CLOCK Proteins
  • Clock protein, mouse
  • RNA Polymerase II

Associated data

  • GEO/GSE39860