Journal of Biological Chemistry
Volume 278, Issue 6, 7 February 2003, Pages 4035-4040
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GENES: STRUCTURE AND REGULATION
The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone Methylation*

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DNA methylation plays an important role in mammalian development and correlates with chromatin-associated gene silencing. The recruitment of MeCP2 to methylated CpG dinucleotides represents a major mechanism by which DNA methylation can repress transcription. MeCP2 silences gene expression partly by recruiting histone deacetylase (HDAC) activity, resulting in chromatin remodeling. Here, we show that MeCP2 associates with histone methyltransferase activity in vivo and that this activity is directed against Lys9 of histone H3. Two characterized repression domains of MeCP2 are involved in tethering the histone methyltransferase to MeCP2. We asked if MeCP2 can deliver Lys9 H3 methylation to the H19 gene, whose activity it represses. We show that the presence of MeCP2 on nucleosomes within the repressor region of the H19 gene (the differentially methylated domain) coincides with an increase in H3 Lys9methylation. Our data provide evidence that MeCP2 reinforces a repressive chromatin state by acting as a bridge between two global epigenetic modifications, DNA methylation and histone methylation.

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Published, JBC Papers in Press, November 11, 2002, DOI 10.1074/jbc.M210256200

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The research in the Tony Kouzarides lab is supported by a program grant from the Cancer Research Campaign.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to this work.

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Supported by the Belgian Fonds National de la Recherche Scientifique (Chargé de recherches du FNRS). Present address: Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, 808 route de Lennik, 1070 Brussels, Belgium.