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Science. 2007 Oct 19;318(5849):447-50. Epub 2007 Aug 30.

Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination.

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1
Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.

Abstract

Methylation of histone H3 lysine 27 (H3K27) is a posttranslational modification that is highly correlated with genomic silencing. Here we show that human UTX, a member of the Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of HOX gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 1 and the monoubiquitination of histone H2A. Moreover, UTX associates with mixed-lineage leukemia (MLL) 2/3 complexes, and during retinoic acid signaling events, the recruitment of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4. Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX.

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PMID:
17761849
DOI:
10.1126/science.1149042
[Indexed for MEDLINE]
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