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Originally published in Science Express on 30 August 2007
Science 19 October 2007:
Vol. 318. no. 5849, pp. 447 - 450
DOI: 10.1126/science.1149042
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Reports

Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination

Min Gyu Lee,1 Raffaella Villa,2 Patrick Trojer,3 Jessica Norman,1 Kai-Ping Yan,1 Danny Reinberg,3 Luciano Di Croce,2 Ramin Shiekhattar1,2*

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.

1 The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
2 Institució Catalana de Recerca i Estudis Avançats and Centre de Regulació Genòmica, Barcelona, Spain.
3 Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.

* To whom correspondence should be addressed. E-mail: ramin.shiekhattar{at}crg.es

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Science. ISSN 0036-8075 (print), 1095-9203 (online)