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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 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.

Pubmed ID: 16717091 RIS Download

Mesh terms: ARNTL Transcription Factors | Animals | Basic Helix-Loop-Helix Transcription Factors | CLOCK Proteins | Circadian Rhythm | DNA-Binding Proteins | Enhancer of Zeste Homolog 2 Protein | HeLa Cells | Histones | Humans | Liver | Lysine | Mice | Mice, Inbred BALB C | NIH 3T3 Cells | Polycomb Repressive Complex 2 | Promoter Regions, Genetic | Trans-Activators | Transcription Factors

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM074277
  • Agency: NINDS NIH HHS, Id: R01 NS047141

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