DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci
DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci
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DOI：
10.1038/77023
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发表时间：
2000-07-01
期刊：
影响因子：
30.8
通讯作者：
Baylin, SB
中科院分区：
文献类型：
--
作者：
Rountree, MR;Bachman, KE;Baylin, SB
DNA甲基化可以通过几种转录抑制复合物（包括甲基-CpG结合结构域蛋白（MBD）和组蛋白脱乙酰酶（HDAC））促进转录沉默。我们在这里表明，维持哺乳动物DNA甲基化的主要酶，DNMT 1，也可以建立一个抑制性转录复合物。DNMT 1的非催化氨基末端与HDAC 2和一种新的蛋白质DMAP 1（DNMT 1相关蛋白）结合，并可介导转录抑制。DMAP 1具有内在的转录抑制活性，并与转录辅助抑制因子TSG 101结合。DMAP 1通过在整个S期与DNMT 1的远端N末端相互作用而靶向复制灶，而HDAC 2仅在S期晚期加入DNMT 1和DMAP 1，为复制后组蛋白如何在异染色质中脱乙酰化提供了平台。因此，DNMT 1不仅维持DNA甲基化，而且可以在DNA复制期间以可遗传的方式将转录抑制染色质直接靶向基因组。
DNA methylation can contribute to transcriptional silencing through several transcriptionally repressive complexes, which include methyl-CpG binding domain proteins (MBDs) and histone deacetylases (HDACs). We show here that the chief enzyme that maintains mammalian DNA methylation, DNMT1, can also establish a repressive transcription complex. The non-catalytic amino terminus of DNMT1 binds to HDAC2 and a new protein, DMAP1 (for DNMT1 associated protein), and can mediate transcriptional repression. DMAP1 has intrinsic transcription repressive activity, and binds to the transcriptional co-repressor TSG101. DMAP1 is targeted to replication foci through interaction with the far N terminus of DNMT1 throughout S phase, whereas HDAC2 joins DNMT1 and DMAP1 only during late S phase, providing a platform for how histones may become deacetylated in heterochromatin following replication. Thus, DNMT1 not only maintains DNA methylation, but also may directly target, in a heritable manner, transcriptionally repressive chromatin to the genome during DNA replication.