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

Nan, X and Ng, H H and Johnson, C A and Laherty, C D and Turner, B M and Eisenman, R N and Bird, A (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature, 393 (6683). pp. 386-389. ISSN 0028-0836

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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 development and in repression of viral genomes. The methyl-CpG-binding proteins MeCP1 and MeCP2 interact specifically with methylated DNA and mediate transcriptional repression. Here we study the mechanism of repression by MeCP2, an abundant nuclear protein that is essential for mouse embryogenesis. MeCP2 binds tightly to chromosomes in a methylation-dependent manner. It contains a transcriptional-repression domain (TRD) that can function at a distance in vitro and in vivo. We show that a region of MeCP2 that localizes with the TRD associates with a corepressor complex containing the transcriptional repressor mSin3A and histone deacetylases. Transcriptional repression in vivo is relieved by the deacetylase inhibitor trichostatin A, 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.

Item Type: Article or Abstract
DOI: 10.1038/30764
PubMed ID: 9620804
Keywords or MeSH Headings: Acetylation; Amino Acid Sequence; Animals; Chromosomal Proteins, Non-Histone; DNA Methylation; DNA-Binding Proteins/metabolism; Dinucleoside Phosphates/metabolism; Enzyme Inhibitors/pharmacology; Gene Expression Regulation/drug effects; Histone Deacetylases/antagonists & inhibitors/metabolism; Histones/metabolism; Hydroxamic Acids/pharmacology; L Cells (Cell Line); Methyl-CpG-Binding Protein 2; Mice; Molecular Sequence Data; Protein Binding; Recombinant Fusion Proteins/metabolism; Repressor Proteins/metabolism; Transcription, Genetic; Transfection;
Subjects: Molecules > Proteins > Transcription factors
Cellular and Organismal Processes > Genetic processes > Transcription
Depositing User: Library Staff
Date Deposited: 25 Nov 2008 21:56
Last Modified: 07 May 2010 20:44

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