The role of DNA methylation in setting up chromatin structure during development

被引:270
作者
Hashimshony, T
Zhang, JM
Keshet, I
Bustin, M
Cedar, H
机构
[1] Hebrew Univ Jerusalem, Dept Cellular Biochem & Human Genet, IL-91120 Jerusalem, Israel
[2] Hebrew Univ Jerusalem, Dept Expt Med & Canc Res, IL-91120 Jerusalem, Israel
[3] NCI, Prot Sect, Mol Carcinogenesis Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/ng1158
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
DNA methylation inhibits gene expression in animal cells, probably by affecting chromatin structure. Biochemical studies suggest that this process may be mediated by methyl-specific binding proteins that recruit enzymatic machinery capable of locally altering histone modification(1). To test whether DNA methylation actually has a role in the assembly of chromatin during normal development, we used cell transfection and a transgene construct genetically programmed to be either methylated or unmethylated in all cell types of the mouse(2). Chromatin immunoprecipitation (ChIP) analysis shows that the presence of DNA methylation brings about the deacetylation of histone H4 and methylation of Lys9 of histone H3 (H3 Lys9) and prevents methylation of Lys4 of histone H3 (H3 Lys4), thus generating a structure identical to that of methylated sequences in the genome. These results indicate that the methylation pattern established in early embryogenesis is profoundly important in setting up the structural profile of the genome.
引用
收藏
页码:187 / 192
页数:6
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