CLOCK:BMAL1 is a pioneer-like transcription factor
- Howard Hughes Medical Institute, National Center for Behavioral Genomics, Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA
Abstract
The mammalian circadian clock relies on the master genes CLOCK and BMAL1 to drive rhythmic gene expression and regulate biological functions under circadian control. Here we show that rhythmic CLOCK:BMAL1 DNA binding promotes rhythmic chromatin opening. Mechanisms include CLOCK:BMAL1 binding to nucleosomes and rhythmic chromatin modification; e.g., incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLOCK:BMAL1, suggesting that the activity of these other transcription factors contributes to the genome-wide CLOCK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation.
Keywords
- circadian rhythms
- regulation of transcription
- nucleosome positioning
- nucleosome occupancy
- MNase-seq
- chromatin modifications
- H2A.Z
Footnotes
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↵2 Corresponding authors
E-mail rosbash{at}brandeis.edu
E-mail menet{at}bio.tamu.edu
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.228536.113.
- Received August 18, 2013.
- Accepted November 27, 2013.
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