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首页> 外文期刊>Nature >Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex (see comments)
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Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex (see comments)

机译：甲基CpG结合蛋白MeCP2对转录的抑制作用涉及组蛋白脱乙酰基酶复合物（参见评论）

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摘要

Cytosine residues in the sequence 5'CpG (cytosine-guanine) are often postsynthetically methylated in animal genomes. CpG methylation is involved in long-term silencing of certain genes during mammalian development and in repression of viral genomes. The methyl-CpG-binding proteins MeCP1 and MeCP2 interact specifically with methylated DNA and mediate transcriptional repression. Here we study the mechanism of repression by MeCP2, an abundant nuclear protein that is essential for mouse embryogenesis. MeCP2 binds tightly to chromosomes in a methylation-dependent manner. It contains a transcriptional-repression domain (TRD) that can function at a distance in vitro and in vivo. We show that a region of MeCP2 that localizes with the TRD associates with a corepressor complex containing the transcriptional repressor mSin3A and histone deacetylases. Transcriptional repression in vivo is relieved by the deacetylase inhibitor trichostatin A, indicating that deacetylation of histones (and/or of other proteins) is an essential component of this repression mechanism. The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2.
机译：序列5'CpG（胞嘧啶-鸟嘌呤）中的胞嘧啶残基通常在动物基因组中被后合成甲基化。 CpG甲基化参与哺乳动物发育过程中某些基因的长期沉默以及病毒基因组的抑制。甲基CpG结合蛋白MeCP1和MeCP2与甲基化的DNA特异性相互作用并介导转录抑制。在这里，我们研究了MeCP2的抑制机制，MeCP2是一种丰富的核蛋白，对小鼠胚胎发生至关重要。 MeCP2以甲基化依赖性方式与染色体紧密结合。它包含一个转录抑制域（TRD），可以在体内和体外保持一定距离。我们显示，MeCP2的区域与TRD本地化与包含转录阻遏物mSin3A和组蛋白脱乙酰基酶的corepressor复杂。脱乙酰酶抑制剂曲古抑菌素A减轻了体内的转录抑制作用，表明组蛋白（和/或其他蛋白质）的脱乙酰作用是该抑制机制的重要组成部分。数据表明，基因调控的两个全局机制，即DNA甲基化和组蛋白脱乙酰化，可以通过MeCP2连接。

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