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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.

Author information

1
Department of Biology, Center for Biological Clocks Research, Texas A&M University, College Station, Texas 77843, USA.
2
Program of Genetics, Texas A&M University, College Station, Texas 77843, USA.
3
Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
4
Department of Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
5
Center for Bioinformatics and Genomic Systems Engineering (CBGSE), Texas A&M AgriLife Research, College Station, Texas 77845, USA.
6
AgriLife Genomics and Bioinformatics, Texas A&M AgriLife Research, College Station, Texas 77845, USA.

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.

KEYWORDS:

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

PMID:
30804225
PMCID:
PMC6411008
DOI:
10.1101/gad.322198.118
[Indexed for MEDLINE]
Free PMC Article

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