Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination

Gyu Lee Min, Raffaella Villa, Patrick Trojer, Jessica Norman, Kai Ping Yan, Danny Reinberg, Luciano Di Croce, Ramin Shiekhattar

Research output: Contribution to journalArticle

518 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)447-450
Number of pages4
JournalScience
Volume318
Issue number5849
DOIs
StatePublished - Oct 19 2007
Externally publishedYes

ASJC Scopus subject areas

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    Min, G. L., Villa, R., Trojer, P., Norman, J., Yan, K. P., Reinberg, D., Di Croce, L., & Shiekhattar, R. (2007). Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science, 318(5849), 447-450. https://doi.org/10.1126/science.1149042