Margot J B, Cardoso M C, Leonhardt H
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
J Cell Biochem. 2001;83(3):373-9. doi: 10.1002/jcb.1236.
In mammalian cells, DNA methylation patterns are precisely maintained after DNA replication with defined changes occurring during development. The major DNA methyltransferase (Dnmt1) is associated with nuclear replication sites during S-phase, which is consistent with a role in maintenance methylation. The subcellular distribution of the recently discovered de novo DNA methyltransferases, Dnmt3a and Dnmt3b, was investigated by immunofluorescence and by epitope tagging. We now show that both Dnmt3a and Dnmt3b are distributed throughout the nucleoplasm but are not associated with nuclear DNA replication sites during S-phase. These results suggest that de novo methylation by Dnmt3a and Dnmt3b occurs independently of the replication process and might involve an alternative mechanism for accessing the target DNA. The different subcellular distribution of mammalian DNA methyltransferases might thus contribute to the regulation of DNA methylation.
在哺乳动物细胞中，DNA甲基化模式在DNA复制后被精确维持，同时在发育过程中会发生特定的变化。主要的DNA甲基转移酶（Dnmt1）在S期与核复制位点相关联，这与它在维持甲基化中的作用相一致。通过免疫荧光和表位标记研究了最近发现的从头DNA甲基转移酶Dnmt3a和Dnmt3b的亚细胞分布。我们现在表明，Dnmt3a和Dnmt3b都分布在整个核质中，但在S期不与核DNA复制位点相关联。这些结果表明，Dnmt3a和Dnmt3b介导的从头甲基化独立于复制过程发生，可能涉及一种访问靶DNA的替代机制。因此，哺乳动物DNA甲基转移酶不同的亚细胞分布可能有助于DNA甲基化的调控。
