Abstract
Methylation of DNA at the dinucleotide CpG is essential for mammalian development and is correlated with stable transcriptional silencing1,2,3. This transcriptional silencing has recently been linked at a molecular level to histone deacetylation through the demonstration of a physical association between histone deacetylases and the methyl CpG-binding protein MeCP2 (refs 4,5). We previously purified a histone deacetylase complex from Xenopus laevis egg extracts that consists of six subunits, including an Rpd3-like deacetylase, the RbA p48/p46 histone-binding protein and the nucleosome-stimulated ATPase Mi-2 (ref. 6). Similar species were subsequently isolated from human cell lines7,8,9, implying functional conservation across evolution. This complex represents the most abundant form of deacetylase in amphibian eggs and cultured mammalian cells6,7,8,9. Here we identify the remaining three subunits of this enzyme complex. One of them binds specifically to methylated DNA in vitro and molecular cloning reveals a similarity to a known methyl CpG-binding protein. Our data substantiate the mechanistic link between DNA methylation, histone deacetylation and transcriptional silencing.
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Acknowledgements
We thank Y. Toh for anti-MTA1 antisera and B. Hendrich for plasmids for expression of recombinant mouse Mbd2b and Mbd3. Protein sequence determination was performed by the Protein/DNA Technology Center of the Rockefeller University. E.B. was supported by a fellowship from the Ministerio de Educacion y Cultura, Spain. P.L.J. was supported by a PRAT fellowship, NIGMS, NIH.
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Wade, P., Gegonne, A., Jones, P. et al. Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet 23, 62–66 (1999). https://doi.org/10.1038/12664
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DOI: https://doi.org/10.1038/12664
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