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Telling Time with Polycomb Proteins

The mouse circadian clock is driven by interacting positive and negative transcriptional feedback loops. As with most genes, this transcriptional regulation is controlled by changes in chromatin structure due to post-translational modifications of histones. Previous studies have shown that H3 acylation occurs at circadian promoters.

Following this lead, Jean-Pierre Etchegaray and colleagues examined the importance of histone methylation by the polycomb group proteins in the mouse circadian clock mechanism. The researchers discovered that endogenous EZH2, a polycomb group enzyme that methylates lysine 27 on H3, co-immunoprecipitates with the CLOCK·BMAL1 circadian transcription complex. Furthermore, transfection of cells in culture with an RNA interfering sequence targeting EZH2 disrupts serum-induced circadian rhythms. These results indicate that EZH2 is important for the maintenance of circadian rhythms, and they extend the activity of the polycomb group proteins to the core clockwork mechanism of mammals.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 21209-21215

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