1. Coactivator-Dependent Oscillation of Chromatin Accessibility Dictates Circadian Gene Amplitude via REV-ERB Loading.
- Author
-
Zhu, Bokai, Gates, Leah A., Stashi, Erin, Dasgupta, Subhamoy, Gonzales, Naomi, Dean, Adam, Dacso, Clifford C., York, Brian, and O’Malley, Bert W.
- Subjects
- *
DNA condensation , *NUCLEOPROTEINS , *CHROMOSOMES , *CHROMATIN , *GENOMES - Abstract
Summary A central mechanism for controlling circadian gene amplitude remains elusive. We present evidence for a “facilitated repression (FR)” model that functions as an amplitude rheostat for circadian gene oscillation. We demonstrate that ROR and/or BMAL1 promote global chromatin decondensation during the activation phase of the circadian cycle to actively facilitate REV-ERB loading for repression of circadian gene expression. Mechanistically, we found that SRC-2 dictates global circadian chromatin remodeling through spatial and temporal recruitment of PBAF members of the SWI/SNF complex to facilitate loading of REV-ERB in the hepatic genome. Mathematical modeling highlights how the FR model sustains proper circadian rhythm despite fluctuations of REV-ERB levels. Our study not only reveals a mechanism for active communication between the positive and negative limbs of the circadian transcriptional loop but also establishes the concept that clock transcription factor binding dynamics is perhaps a central tenet for fine-tuning circadian rhythm. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF