Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1
Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1
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DOI：
10.1074/jbc.m209923200
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发表时间：
2003-02-14
影响因子：
4.8
通讯作者：
Shiota, K
中科院分区：
文献类型：
--
作者：
Kimura, H;Shiota, K
在哺乳动物细胞分裂过程中，DNA甲基化模式被准确地转移到新合成的DNA链上。这取决于DNA甲基转移酶活性的维持。DNA甲基化可以通过组蛋白去乙酰化酶（HDAC）的募集影响染色质组织和基因表达。在这里，我们表明，甲基CpG结合蛋白，MeCP 2，直接与维护DNA甲基转移酶，Dnmt 1相互作用。与Dnmt 1相互作用的MeCP 2区域对应于转录阻遏物结构域，其也可以通过辅阻遏物mSin 3A募集HDAC。Dnmt 1可以与HDAC以及MeCP 2形成复合物。令人惊讶的是，MeCP 2-Dnmt 1复合物不含组蛋白脱乙酰酶HDAC 1。因此，Dnmt 1取代了mSin 3A-HDAC 1复合物，表明MeCP 2相互作用的Dnmt 1不与HDAC 1结合。此外，我们证明了MeCP 2可以与半甲基化以及完全甲基化的DNA形成复合物。免疫沉淀的MeCP 2复合物显示出对半甲基化DNA的DNA甲基转移酶活性。这些结果表明，Dnmt 1与MeCP 2相关联，以便在体内进行维持甲基化。我们建议，全基因组和/或特定的本地DNA甲基化可能会保持Dnmt 1-MeCP 2复合物，绑定到半甲基化的DNA。Dnmt 1可以通过多个步骤募集到靶向区域，这些步骤可能涉及或可能不涉及组蛋白脱乙酰酶。
During mammalian cell division, DNA methylation patterns are transferred accurately to the newly synthesized DNA strand. This depends on maintenance DNA methyltransferase activity. DNA methylation can affect chromatin organization and gene expression by recruitment of histone deacetylases (HDACs). Here we show that the methyl-CpG binding protein, MeCP2, interacts directly with the maintenance DNA methyltransferase, Dnmt1. The region of MeCP2 that interacts with Dnmt1 corresponds to the transcription repressor domain which can also recruit HDACs via a corepressor, mSin3A. Dnmt1 can form complexes with HDACs as well as MeCP2. Surprisingly, the MeCP2-Dnmt1 complex does not contain the histone deacetylase, HDAC1. Thus, Dnmt1 takes the place of the mSin3A-HDAC1 complex, indicating that the MeCP2-interacting Dnmt1 does not bind to HDAC1. Further, we demonstrate that MeCP2 can form a complex with hemimethylated as well as fully methylated DNA. Immunoprecipitated MeCP2 complexes show DNA methyltransferase activity to hemimethylated DNA. These results suggest that Dnmt1 associates with MeCP2 in order to perform maintenance methylation in vivo. We propose that genome-wide and/or -specific local DNA methylation may be maintained by the Dnmt1-MeCP2 complexes, bound to hemimethylated DNA. Dnmt1 may be recruited to targeted regions via multiple steps that may or may not involve histone deacetylases.