Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation

Methylation of DNA at the dinucleotide CpG is essential for mammalian development and is correlated with stable transcriptional silencing(1-3). This transcriptional silencing has recently been linked at a molecular level to histone deacetylation MeCP2 (refs 4,5). We previously purified a histone deacetylase through the demonstration of a physical association between histone deacetylases and the methyl CpG-binding protein 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 lines(7-9), implying functional conservation across evolution. This complex represents the most abundant form of deacetylase in amphibian eggs and cultured mammalian cells(6-9). Here we identify the remaining three subunits of this across 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.