title: Coactivator-Dependent Oscillation of Chromatin Accessibility Dictates Circadian Gene Amplitude via REV-ERB Loading.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
authors.forename: Bokai
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Gates
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
authors.forename: Erin
authors.initials: E
authors.lastname: Stashi
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
authors.forename: Subhamoy
authors.initials: S
authors.lastname: Dasgupta
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
authors.forename: Naomi
authors.initials: N
authors.lastname: Gonzales
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
authors.forename: Adam
authors.initials: A
authors.lastname: Dean
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.|Department of Medicine, Baylor College of Medicine, Houston, TX.
authors.forename: Clifford C
authors.initials: CC
authors.lastname: Dacso
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Brian
authors.initials: B
authors.lastname: York
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D002940:Circadian Rhythm; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000378:metabolism*; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D002843:Chromatin; C498262:Nr1d1 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539739:Rora protein, mouse