Tissue-specific BMAL1 cistromes reveal that rhythmic transcription is associated with rhythmic enhancer–enhancer interactions

Joshua R. Beytebiere, Alexandra J. Trott, Ben J. Greenwell, Collin A. Osborne, Helene Vitet, Jessica Spence, Seung Hee Yoo, Zheng Chen, Joseph S. Takahashi, Noushin Ghaffari, Jerome S. Menet

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of thousands of genes. Consistent with the various biological functions under clock control, rhythmic gene expression is tissue-specific despite an identical clockwork mechanism in every cell. Here we show that BMAL1 DNA binding is largely tissue-specific, likely because of differences in chromatin accessibility between tissues and cobinding of tissue-specific transcription factors. Our results also indicate that BMAL1 ability to drive tissue-specific rhythmic transcription is associated with not only the activity of BMAL1-bound enhancers but also the activity of neighboring enhancers. Characterization of physical interactions between BMAL1 enhancers and other cis-regulatory regions by RNA polymerase II chromatin interaction analysis by paired-end tag (ChIA-PET) reveals that rhythmic BMAL1 target gene expression correlates with rhythmic chromatin interactions. These data thus support that much of BMAL1 target gene transcription depends on BMAL1 capacity to rhythmically regulate a network of enhancers.

Original languageEnglish (US)
Pages (from-to)294-309
Number of pages16
JournalGenes and Development
Issue number5-6
StatePublished - Mar 1 2019
Externally publishedYes


  • Circadian clock
  • Enhancer
  • Enhancer interactions
  • Tissue-specific cistromes
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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