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

59 Scopus citations

Abstract

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
Volume33
Issue number5-6
DOIs
StatePublished - Mar 1 2019

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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