title: The Catalytic and Non-catalytic Functions of the Brahma Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in Drosophila.
abstract: Daily rhythms in gene expression play a critical role in the progression of circadian clocks, and are under regulation by transcription factor binding, histone modifications, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Although previous studies have shown that clock-controlled genes exhibit rhythmic chromatin modifications, less is known about the functions performed by chromatin remodelers in animal clockwork. Here we have identified the Brahma (Brm) complex as a regulator of the Drosophila clock. In Drosophila, CLOCK (CLK) is the master transcriptional activator driving cyclical gene expression by participating in an auto-inhibitory feedback loop that involves stimulating the expression of the main negative regulators, period (per) and timeless (tim). BRM functions catalytically to increase nucleosome density at the promoters of per and tim, creating an overall restrictive chromatin landscape to limit transcriptional output during the active phase of cycling gene expression. In addition, the non-catalytic function of BRM regulates the level and binding of CLK to target promoters and maintains transient RNAPII stalling at the per promoter, likely by recruiting repressive and pausing factors. By disentangling its catalytic versus non-catalytic functions at the promoters of CLK target genes, we uncovered a multi-leveled mechanism in which BRM fine-tunes circadian transcription.
authors.affiliation: Department of Entomology and Nematology, College of Agricultural and Environmental Sciences, University of California, Davis, Davis, California, United States of America.
authors.forename: Rosanna S
authors.initials: RS
authors.lastname: Kwok
authors.affiliation: Department of Entomology and Nematology, College of Agricultural and Environmental Sciences, University of California, Davis, Davis, California, United States of America.
authors.forename: Ying H
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Entomology and Nematology, College of Agricultural and Environmental Sciences, University of California, Davis, Davis, California, United States of America.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Lei
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers, the State University of New Jersey, Piscataway, New Jersey, United States of America.
authors.forename: Isaac
authors.initials: I
authors.lastname: Edery
authors.affiliation: Department of Entomology and Nematology, College of Agricultural and Environmental Sciences, University of California, Davis, Davis, California, United States of America.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Chiu
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D056926:CLOCK Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C120526:Clk protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D015534:Trans-Activators; C086469:brm protein, Drosophila; C096445:tim protein, Drosophila; D056926:CLOCK Proteins; D012319:RNA Polymerase II