Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex

Xinsheng Nan, Huck-Hui Ng, Colin A. Johnson, Carol D. Laherty, Bryan M. Turner, Robert N. Eisenman and Adrian Bird ()
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Xinsheng Nan: Institute of Cell and Molecular Biology, University of Edinburgh
Huck-Hui Ng: Institute of Cell and Molecular Biology, University of Edinburgh
Colin A. Johnson: The Medical School, University of Birmingham
Carol D. Laherty: Fred Hutchinson Cancer Research Center
Bryan M. Turner: The Medical School, University of Birmingham
Robert N. Eisenman: Fred Hutchinson Cancer Research Center
Adrian Bird: Institute of Cell and Molecular Biology, University of Edinburgh

Nature, 1998, vol. 393, issue 6683, 386-389

Abstract: Abstract Cytosine residues in the sequence 5′CpG (cytosine–guanine) are often postsynthetically methylated in animal genomes. CpG methylation is involved in long-term silencing of certain genes during mammalian development1,2 and in repression of viral genomes3,4. The methyl-CpG-binding proteins MeCP1 (ref. 5) and MeCP2 (ref. 6) interact specifically with methylated DNA and mediate transcriptional repression7,8,9. Here we study the mechanism of repression by MeCP2, an abundant nuclear protein that is essential for mouse embryogenesis10. MeCP2 binds tightly to chromosomes in a methylation-dependent manner11,12. It contains a transcriptional-repression domain (TRD) that can function at a distance in vitro and in vivo9. We show that a region of MeCP2 that localizes with the TRD associates with a corepressor complex containing the transcriptional repressor mSin3A and histone deacetylases13,14,15,16,17,18,19. Transcriptional repression in vivo is relieved by the deacetylase inhibitor trichostatin A20, indicating that deacetylation of histones (and/or of other proteins) is an essential component of this repression mechanism. The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2.

Date: 1998
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DOI: 10.1038/30764

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