Temporal orchestration of repressive chromatin modifiers by circadian clock Period complexes

HA Duong, CJ Weitz - Nature structural & molecular biology, 2014 - nature.com
Nature structural & molecular biology, 2014nature.com
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 …
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.
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