Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription
Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription
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DOI：
10.1093/emboj/20.10.2536
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发表时间：
2001-05-15
期刊：
影响因子：
11.4
通讯作者：
Kouzarides, T
中科院分区：
文献类型：
--
作者：
Fuks, F;Burgers, WA;Kouzarides, T
Dnmt3a DNA甲基转移酶对哺乳动物的发育至关重要，并负责基因组甲基化模式的产生，从而导致转录沉默。在这里，我们发现Dnmt3a与RP58结合，RP58是一种在转录沉默的异染色质上发现的dna结合转录抑制蛋白。Dnmt3a作为RP58的辅抑制因子，不需要其从头甲基转移酶活性。与其他表征的共抑制因子一样，Dnmt3a通过其atrx同源结构域与组蛋白去乙酰化酶HDAC1结合。Dnmt3a的这个结构域代表了一个独立的转录抑制结构域，其沉默功能需要HDAC活性。这些结果确定了Dnmt3a是一种携带去乙酰化酶活性的协同抑制蛋白，并表明Dnmt3a可以通过与dna结合转录因子的关联来靶向特定的调控灶。
The Dnmt3a DNA methyltransferase is essential for mammalian development and is responsible for the generation of genomic methylation patterns, which lead to transcriptional silencing. Here, we show that Dnmt3a associates with RP58, a DNA-binding transcriptional repressor protein found at transcriptionally silent heterochromatin. Dnmt3a acts as a corepressor for RP58 in a manner that does not require its de novo methyltransferase activity. Like other characterized co-repressors, Dnmt3a associates with the histone deacetylase HDAC1 using its ATRX-homology domain. This domain of Dnmt3a represents an independent transcriptional repressor domain whose silencing functions require HDAC activity. These results identify Dnmt3a as a co-repressor protein carrying deacetylase activity and show that Dnmt3a can be targeted to specific regulatory foci via its association with DNA-binding transcription factors.