title: Temporal orchestration of repressive chromatin modifiers by circadian clock Period complexes.
abstract: The mammalian circadian clock is built on a molecular feedback loop in which the Period (PER) proteins, acting in a large, poorly understood complex, repress Clock-Bmal1, the transcription factor driving their expression. We found that mouse PER complexes include the histone methyltransferase HP1γ-Suv39h. PER proteins recruited HP1γ-Suv39h to the Per1 and Per2 promoters, and HP1γ-Suv39h proved important for circadian di- and trimethylation of histone H3 Lys9 (H3K9) at the Per1 promoter, feedback repression and clock function. HP1γ-Suv39h was recruited to the Per1 and Per2 promoters ~4 h after recruitment of HDAC1, a PER-associated protein previously implicated in clock function and H3K9 deacetylation at the Per1 promoter. PER complexes containing HDAC1 or HP1γ-Suv39h appeared to be physically separable. Circadian clock negative feedback by the PER complex thus involves dynamic, ordered recruitment of repressive chromatin modifiers to DNA-bound Clock-Bmal1.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hao A
authors.initials: HA
authors.lastname: Duong
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Weitz
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics*; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D056950:Period Circadian Proteins; D012097:Repressor Proteins; D000090266:Chromobox Protein Homolog 5; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1