DNA methyltransferase Dnmt1 associates with histone deacetylase activity
DNA methyltransferase Dnmt1 associates with histone deacetylase activity
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DOI：
10.1038/71750
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发表时间：
2000-01-01
期刊：
影响因子：
30.8
通讯作者：
Kouzarides, T
中科院分区：
文献类型：
--
作者：
Fuks, F;Burgers, WA;Kouzarides, T
DNA甲基化酶Dnmt1在哺乳动物中负责胞嘧啶甲基化，并在基因沉默中发挥作用（1-4）。DNA甲基化抑制基因的部分原因是甲基- cpg结合蛋白MeCP2的募集，MeCP2反过来募集组蛋白去乙酰化酶活性（5,6）。在这里，我们发现Dnmt1本身与体内组蛋白去乙酰化酶活性相关。与这种关联一致，我们发现一种已知的组蛋白去乙酰化酶HDAC1具有结合Dnmt1的能力，并且可以从核提取物中纯化甲基转移酶活性。我们已经在Dnmt1中发现了一个转录抑制域，至少部分地通过募集组蛋白去乙酰化酶活性起作用，并显示出与三胸相关蛋白HRX（也称为MLL和ALL-1）的抑制域同源。我们的数据显示DNA甲基化和组蛋白去乙酰化之间的联系比以前认为的更直接。我们认为Dnmt1介导的DNA甲基化过程可能依赖于或通过组蛋白去乙酰化酶活性产生染色质状态的改变。
The DNA methyltransferase Dnmt1 is responsible for cytosine methylation in mammals and has a role in gene silencing(1-4) DNA methylation represses genes partly by recruitment of the methyl-CpG-binding protein MeCP2, which in turn recruits a histone deacetylase activity(5,6). Here we show that Dnmt1 is itself associated with histone deacetylase activity in vivo. Consistent with this association, we find that one of the known histone deacetylases, HDAC1, has the ability to bind Dnmt1 and can purify methyltransferase activity from nuclear extracts. We have identified a transcriptional repression domain in Dnmt1 that functions, at least partly, by recruiting histone deacetylase activity and shows homology to the repressor domain of the trithorax-related protein HRX (also known as MLL and ALL-1). Our data show a more direct connection between DNA methylation and histone deacetylation than was previously considered. We suggest that the process of DNA methylation, mediated by Dnmt1, may depend on or generate an altered chromatin state via histone deacetylase activity.