CLOCK:BMAL1 is a pioneer-like transcription factor

Genes Dev. 2014 Jan 1;28(1):8-13. doi: 10.1101/gad.228536.113.


The mammalian circadian clock relies on the master genes CLOCK and BMAL1 to drive rhythmic gene expression and regulate biological functions under circadian control. Here we show that rhythmic CLOCK:BMAL1 DNA binding promotes rhythmic chromatin opening. Mechanisms include CLOCK:BMAL1 binding to nucleosomes and rhythmic chromatin modification; e.g., incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLOCK:BMAL1, suggesting that the activity of these other transcription factors contributes to the genome-wide CLOCK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation.

Keywords: H2A.Z; MNase-seq; chromatin modifications; circadian rhythms; nucleosome occupancy; nucleosome positioning; regulation of transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism*
  • Animals
  • CLOCK Proteins / genetics
  • CLOCK Proteins / metabolism*
  • Chromatin Assembly and Disassembly
  • Circadian Rhythm / physiology*
  • Gene Expression Regulation
  • Mice
  • Nucleosomes / metabolism
  • Protein Binding
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Nucleosomes
  • Transcription Factors
  • CLOCK Proteins
  • Clock protein, mouse