Tissue-specific BMAL1 cistromes reveal that rhythmic transcription is associated with rhythmic enhancer-enhancer interactions. Academic Article uri icon


  • 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.

published proceedings

  • Genes Dev

altmetric score

  • 15

author list (cited authors)

  • Beytebiere, J. R., Trott, A. J., Greenwell, B. J., Osborne, C. A., Vitet, H., Spence, J., ... Menet, J. S.

citation count

  • 69

complete list of authors

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

publication date

  • March 2019