Coactivator-Dependent Oscillation of Chromatin Accessibility Dictates Circadian Gene Amplitude via REV-ERB Loading
Zhu, B.;Gates, L. A.;Stashi, E.;Dasgupta, S.;Gonzales, N.;Dean, A.;Dacso, C. C.;York, B.;O'Malley, B. W. (2015). "Coactivator-Dependent Oscillation of Chromatin Accessibility Dictates Circadian Gene Amplitude via REV-ERB Loading." Molecular Cell 60 5: 769-83
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.
ISSN: 1097-4164 (Electronic);1097-2765 (Linking)
Accession Number: 26611104