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Genes Dev. 2019 Mar 1;33(5-6):294-309. doi: 10.1101/gad.322198.118. Epub 2019 Feb 25.

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

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Department of Biology, Center for Biological Clocks Research, Texas A&M University, College Station, Texas 77843, USA.
Program of Genetics, Texas A&M University, College Station, Texas 77843, USA.
Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Department of Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Center for Bioinformatics and Genomic Systems Engineering (CBGSE), Texas A&M AgriLife Research, College Station, Texas 77845, USA.
AgriLife Genomics and Bioinformatics, Texas A&M AgriLife Research, College Station, Texas 77845, USA.


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.


circadian clock; enhancer–enhancer interactions; tissue-specific cistromes; transcription

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