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Originally published in Science Express on 26 September 2002
Science 1 November 2002:
Vol. 298. no. 5595, pp. 1039 - 1043
DOI: 10.1126/science.1076997
Prev | Table of Contents

Reports

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

Ru Cao,12 Liangjun Wang,3 Hengbin Wang,1 Li Xia,1 Hediye Erdjument-Bromage,4 Paul Tempst,4 Richard S. Jones,3 Yi Zhang12*

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.

1 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center,
2 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
3 Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA.
4 Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
*   To whom correspondence should be addressed. E-mail: yi_zhang{at}med.unc.edu

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Nucleic Acids Res. 34, 3555-3567
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Suz12 binds to silenced regions of the genome in a cell-type-specific manner.
S. L. Squazzo, H. O'Geen, V. M. Komashko, S. R. Krig, V. X. Jin, S.-w