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Journal of Biological Chemistry
Article . 2006 . Peer-reviewed
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Journal of Biological Chemistry
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The Polycomb Group Protein EZH2 Is Required for Mammalian Circadian Clock Function

Authors: Etchegaray, Jean-Pierre; Yang, Xiaoming; DeBruyne, Jason P.; Peters, Antoine H.F.M.; Weaver, David R.; Jenuwein, Thomas; Reppert, Steven M.;

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

Abstract

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.

Country
United States
Keywords

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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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    164
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
164
Top 1%
Top 10%
Top 10%
gold