DOI: 10.1126/science.1149042. Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination

Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination

10.1126/science.1149042

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

Lee, M. G., 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), 447â450.

Authors 8

Min Gyu Lee (first)
Raffaella Villa (additional)
Patrick Trojer (additional)
Jessica Norman (additional)
Kai-Ping Yan (additional)
Danny Reinberg (additional)
Luciano Di Croce (additional)
Ramin Shiekhattar (additional)

References 29 Referenced 640

10.1016/j.tig.2003.09.007
10.1038/nrm1761
10.1016/S0959-437X(02)00287-3
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10.1074/jbc.M603722200
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Materials and methods are available as supporting material on Science Online.
We thank A. Shilatifard and T. Jenuwein for their antibodies; Kazusa DNA Research Institute Foundation for UTX cDNA; M. Hart T. Beer K. Speicher and D. Speicher for help with mass spectrometry; G. Harris for figure preparation; and H. Hoff and D. Schultz for protein expression. L.D.C. was supported by a grant from the Spanish–Ministerio de Educación y Cultura and R.S. was supported by a grant from NIH (RO1CA090758) and an intramural fund from Centre de Regulació Genòmica.

Dates

Type	When
Created	18 years ago (Aug. 30, 2007, 9:15 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 3:11 a.m.)
Indexed	3 days, 2 hours ago (Sept. 3, 2025, 6:19 a.m.)
Issued	17 years, 10 months ago (Oct. 19, 2007)
Published	17 years, 10 months ago (Oct. 19, 2007)
Published Print	17 years, 10 months ago (Oct. 19, 2007)

Funders 0

None

BibTeX

@article{Lee_2007, title={Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination}, volume={318}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1149042}, DOI={10.1126/science.1149042}, number={5849}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Lee, Min Gyu and Villa, Raffaella and Trojer, Patrick and Norman, Jessica and Yan, Kai-Ping and Reinberg, Danny and Di Croce, Luciano and Shiekhattar, Ramin}, year={2007}, month=oct, pages={447–450} }

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