Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
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DOI：
10.1038/561
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发表时间：
1998-06-01
期刊：
影响因子：
30.8
通讯作者：
Wolffe, AP
中科院分区：
文献类型：
--
作者：
Jones, PL;Veenstra, GJC;Wolffe, AP
脊椎动物中的CpG甲基化与染色质结构和基因沉默的改变相关（1-4）。DNA甲基化状态的差异与印记现象和致癌作用有关（5-10）。在非洲爪蟾卵母细胞中，DNA甲基化通过抑制性核小体阵列的组装而主要沉默转录（11）。组装成染色质的甲基化DNA与转录抑制因子MeCP 2结合，MeCP 2与Sin 3和组蛋白脱乙酰酶共分馏。MeCP 2和甲基化DNA赋予的沉默可以通过抑制组蛋白脱乙酰酶来缓解，从而促进染色质的重塑和转录激活。这些结果建立了DNA甲基化依赖的转录沉默和染色质修饰之间的直接因果关系。
CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing(1-4). Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis(5-10). In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array(11). Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodeling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.