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Originally published in Science Express on 20 March 2003
Science 4 April 2003:
Vol. 300. no. 5616, pp. 131 - 135
DOI: 10.1126/science.1084274
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Reports

Role of Histone H3 Lysine 27 Methylation in X Inactivation

Kathrin Plath,1* Jia Fang,2* Susanna K. Mlynarczyk-Evans,1 Ru Cao,2 Kathleen A. Worringer,1 Hengbin Wang,2 Cecile C. de la Cruz,1 Arie P. Otte,3 Barbara Panning,1dagger Yi Zhang2dagger

The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi.

1 Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.
2 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
3 Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, Netherlands.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: yi_zhang{at}med.unc.edu; bpanning{at}biochem.ucsf.edu

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B. P. Chadwick and H. F. Willard (2003)
Hum. Mol. Genet. 12, 2167-2178
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The Protein Phosphatase-1 (PP1) Regulator, Nuclear Inhibitor of PP1 (NIPP1), Interacts with the Polycomb Group Protein, Embryonic Ectoderm Development (EED), and Functions as a Transcriptional Repressor.
Q. Jin, A. van Eynde, M. Beullens, N. Roy, G. Thiel, W. Stalmans, and M. Bollen (2003)
J. Biol. Chem. 278, 30677-30685
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Heterochromatin and Epigenetic Control of Gene Expression.
S. I. S. Grewal and D. Moazed (2003)
Science 301, 798-802
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Heterochromatin: stable and unstable invasions at home and abroad.
J. A. Fahrner and S. B. Baylin (2003)
Genes & Dev. 17, 1805-1812
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Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27.
J. Min, Y. Zhang, and R.-M. Xu (2003)
Genes & Dev. 17, 1823-1828
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An epigenetic road map for histone lysine methylation.
M. Lachner, R. J. O'Sullivan, and T. Jenuwein (2003)
J. Cell Sci. 116, 2117-2124
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