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</script>The Polycomb Group Protein EZH2 Is Required for Mammalian Circadian Clock Function
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.
- University of Massachusetts Medical School United States
- Vienna Biocenter Austria
- Research Institute of Molecular Pathology Austria
- Friedrich Miescher Institute Switzerland
CLOCK Proteins, Histones, Mice, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Promoter Regions, Genetic, Inbred BALB C, *Circadian Rhythm, Mice, Inbred BALB C, Neuroscience and Neurobiology, Lysine, Polycomb Repressive Complex 2, ARNTL Transcription Factors, Circadian Rhythm, DNA-Binding Proteins, Liver, Hela Cells, NIH 3T3 Cells, Trans-Activators, Promoter Regions (Genetics), HeLa Cells, Transcription Factors
CLOCK Proteins, Histones, Mice, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Promoter Regions, Genetic, Inbred BALB C, *Circadian Rhythm, Mice, Inbred BALB C, Neuroscience and Neurobiology, Lysine, Polycomb Repressive Complex 2, ARNTL Transcription Factors, Circadian Rhythm, DNA-Binding Proteins, Liver, Hela Cells, NIH 3T3 Cells, Trans-Activators, Promoter Regions (Genetics), HeLa Cells, Transcription Factors
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