Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing

American Association for the Advancement of Science (AAAS) - Tập 298 Số 5595 - Trang 1039-1043 - 2002
Ru Cao1,2, Liangjun Wang3, Hengbin Wang4, Li Xia4, Hediye Erdjument‐Bromage5, Paul Tempst5, Richard S. Jones3, Yi Zhang1,4
1Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599–7295, USA.
2Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA
3Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA
4Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center,
5Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021 USA

Tóm tắt

Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27). Using chromatin immunoprecipitation assays, we show that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an Ultrabithorax ( Ubx ) Polycomb response element (PRE), and that this methylation correlates with Ubx repression. Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing.

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We thank T. Nagases T. Magnuson A. Verreault H. Chen A. Otte A. Ullrich K. Bomsztyk and K. Luger for plasmids; H.-H. Ng for yeast histones; T. Jenuwein and P. O'Farrell for antibodies; and E. Henry for critical reading of the manuscript. Y.Z. is a Kimmel Scholar and is supported by grants from the NIH and American Cancer Society. This work was also supported by an NIH grant (to R.S.J.) and a National Cancer Institute grant (to P.T.).

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American Association for the Advancement of Science (AAAS)

Tập 298 Số 5595

1039-1043

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