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Science 318 (5849): 447-450

Copyright © 2007 by the American Association for the Advancement of Science

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*

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.

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}

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SWI/SNF Mediates Polycomb Eviction and Epigenetic Reprogramming of the INK4b-ARF-INK4a Locus.
S. K. Kia, M. M. Gorski, S. Giannakopoulos, and C. P. Verrijzer (2008)
Mol. Cell. Biol. 28, 3457-3464
   Abstract »    Full Text »    PDF »
Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2.
D. Pasini, K. H. Hansen, J. Christensen, K. Agger, P. A.C. Cloos, and K. Helin (2008)
Genes & Dev. 22, 1345-1355
   Abstract »    Full Text »    PDF »
Changes in the Distributions and Dynamics of Polycomb Repressive Complexes during Embryonic Stem Cell Differentiation.
X. Ren, C. Vincenz, and T. K. Kerppola (2008)
Mol. Cell. Biol. 28, 2884-2895
   Abstract »    Full Text »    PDF »
Characterization of Drosophila melanogaster JmjC+N histone demethylases.
M. Lloret-Llinares, C. Carre, A. Vaquero, N. de Olano, and F. Azorin (2008)
Nucleic Acids Res. 36, 2852-2863
   Abstract »    Full Text »    PDF »
Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease.
P. A.C. Cloos, J. Christensen, K. Agger, and K. Helin (2008)
Genes & Dev. 22, 1115-1140
   Abstract »    Full Text »    PDF »

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