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Published Online August 30, 2007
Science DOI: 10.1126/science.1149042

Reports

Submitted on August 10, 2007
Accepted on August 20, 2007

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 Shiekhattar 4*

1 The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, USA.
2 ICREA and Centre de Regulació Genòmica, Barcelona, Spain.
3 Howard Hughes Medical Institute, Department of Biochemistry, NYU School of Medicine, New York, NY, USA.
4 The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, USA.; ICREA and Centre de Regulació Genòmica, Barcelona, Spain.

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

Methylation of histone H3 lysine 27 (H3K27) is a post-translational modification highly correlated with genomic silencing. Here we show that UTX, a member of JmjC-family proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of HOX gene clusters and regulate their transcriptional output by modulating the recruitment of polycomb repressive complex 1 (PRC1) and the monoubiquitination of histone H2A. Moreover, UTX associates with Mixed-Lineage leukemia (MLL) 2/3 complexes, and during retinoic acid signaling event the recruitment of UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of histone H3 lysine 4 (H3K4). Our results uncover a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with demethylation of H3K27 through UTX.


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