Department of Biochemistry, Purdue University, West Lafayette, IN 47907, U.S.A.
Institute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Stuttgart, Germany
Biochem Soc Trans. 2018 Oct 19;46(5):1191-1202. doi: 10.1042/BST20170574. Epub 2018 Aug 28.
As part of the epigenetic network, DNA methylation is a major regulator of chromatin structure and function. In mammals, it mainly occurs at palindromic CpG sites, but asymmetric methylation at non-CpG sites is also observed. Three enzymes are involved in the generation and maintenance of DNA methylation patterns. DNMT1 has high preference for hemimethylated CpG sites, and DNMT3A and DNMT3B equally methylate unmethylated and hemimethylated DNA, and also introduce non-CpG methylation. Here, we review recent observations and novel insights into the structure and function of mammalian DNMTs (DNA methyltransferases), including new structures of DNMT1 and DNMT3A, data on their mechanism, regulation by post-translational modifications and on the function of DNMTs in cells. In addition, we present news findings regarding the allosteric regulation and targeting of DNMTs by chromatin modifications and chromatin proteins. In combination, the recent publications summarized here impressively illustrate the intensity of ongoing research in this field. They provide a deeper understanding of key mechanistic properties of DNMTs, but they also document still unsolved issues, which need to be addressed in future research.
作为表观遗传网络的一部分，DNA 甲基化是染色质结构和功能的主要调节剂。在哺乳动物中，它主要发生在回文 CpG 位点，但也观察到非 CpG 位点的不对称甲基化。三种酶参与 DNA 甲基化模式的产生和维持。DNMT1 对半甲基化的 CpG 位点具有高偏好性，而 DNMT3A 和 DNMT3B 平等地甲基化未甲基化和半甲基化的 DNA，并且还引入非 CpG 甲基化。在这里，我们回顾了哺乳动物 DNMT（DNA 甲基转移酶）的结构和功能的最新观察结果和新见解，包括 DNMT1 和 DNMT3A 的新结构、关于其机制的数据、翻译后修饰的调节以及 DNMTs 在细胞中的功能。此外，我们还介绍了关于 DNMT 由染色质修饰和染色质蛋白的变构调节和靶向的新发现。总的来说，这里总结的最新出版物令人印象深刻地说明了该领域正在进行的研究的强度。它们提供了对 DNMT 关键机制特性的更深入理解，但也记录了仍未解决的问题，需要在未来的研究中解决。
