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Published Online September 26, 2002
Science DOI: 10.1126/science.1076997

Reports

Submitted on August 5, 2002
Accepted on September 9, 2002

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

Ru Cao 1, Liangjun Wang 2, Hengbin Wang 3, Li Xia 3, Hediye Erdjument-Bromage 4, Paul Tempst 4, Richard S. Jones 2, Yi Zhang 1*

1 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
2 Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA.
3 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, 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.

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 a 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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LIN-61, One of Two Caenorhabditis elegans Malignant-Brain-Tumor-Repeat-Containing Proteins, Acts With the DRM and NuRD-Like Protein Complexes in Vulval Development but Not in Certain Other Biological Processes.
M. M. Harrison, X. Lu, and H. R. Horvitz (2007)
Genetics 176, 255-271
   Abstract »    Full Text »    PDF »
Crucial Roles for Chromatin Dynamics in Cellular Memory.
S. Hirose (2007)
J. Biochem. 141, 615-619
   Abstract »    Full Text »    PDF »
Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells.
J. Tan, X. Yang, L. Zhuang, X. Jiang, W. Chen, P. L. Lee, R.K. M. Karuturi, P. B. O. Tan, E. T. Liu, and Q. Yu (2007)
Genes & Dev. 21, 1050-1063
   Abstract »    Full Text »    PDF »
Epigenetic Reprogramming of OCT4 and NANOG Regulatory Regions by Embryonal Carcinoma Cell Extract.
C. T. Freberg, J. A. Dahl, S. Timoskainen, and P. Collas (2007)
Mol. Biol. Cell 18, 1543-1553
   Abstract »    Full Text »    PDF »
Non-mammalian models for epigenetic analyses in cancer.
M. Schaefer, M. Meusburger, and F. Lyko (2007)
Hum. Mol. Genet. 16, R1-R6
   Abstract »    Full Text »    PDF »


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