The Polycomb Group Protein EZH2 Is Required for Mammalian Circadian Clock Function

We examined the importance of histone methylation by the polycomb group proteins in the mouse circadian clock mechanism. Endogenous EZH2, a polycomb group enzyme that methylates lysine 27 on histone H3, co-immunoprecipitates with CLOCK and BMAL1 throughout the circadian cycle in liver nuclear extrac...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-07, Vol.281 (30), p.21209-21215
Main Authors: Etchegaray, Jean-Pierre, Yang, Xiaoming, DeBruyne, Jason P., Peters, Antoine H.F.M., Weaver, David R., Jenuwein, Thomas, Reppert, Steven M.
Format: Article
Language:English
Subjects:
Animals
ARNTL Transcription Factors
Basic Helix-Loop-Helix Transcription Factors - chemistry
Circadian Rhythm
CLOCK Proteins
DNA-Binding Proteins - physiology
Enhancer of Zeste Homolog 2 Protein
HeLa Cells
Histones - chemistry
Humans
Liver - metabolism
Lysine - chemistry
Mice
Mice, Inbred BALB C
NIH 3T3 Cells
Polycomb Repressive Complex 2
Promoter Regions, Genetic
Trans-Activators - metabolism
Transcription Factors - physiology
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Summary:We examined the importance of histone methylation by the polycomb group proteins in the mouse circadian clock mechanism. Endogenous EZH2, a polycomb group enzyme that methylates lysine 27 on histone H3, co-immunoprecipitates with CLOCK and BMAL1 throughout the circadian cycle in liver nuclear extracts. Chromatin immunoprecipitation revealed EZH2 binding and di- and trimethylation of H3K27 on both the Period 1 and Period 2 promoters. A role of EZH2 in cryptochrome-mediated transcriptional repression of the clockwork was supported by overexpression and RNA interference studies. Serum-induced circadian rhythms in NIH 3T3 cells in culture were disrupted by transfection of an RNA interfering sequence targeting EZH2. These results indicate that EZH2 is important for the maintenance of circadian rhythms and extend the activity of the polycomb group proteins to the core clockwork mechanism of mammals.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M603722200