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

被引:671
作者
Wade, PA
Gegonne, A
Jones, PL
Ballestar, E
Aubry, F
Wolffe, AP
机构
[1] NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA
[2] INSERM, U435, F-35042 Rennes, France
基金
美国国家卫生研究院;
关键词
D O I
10.1038/12664
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:62 / 66
页数:5
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