Mammalian DNA methyltransferases: new discoveries and open questions.
Mammalian DNA methyltransferases: new discoveries and open questions.
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DOI：
10.1042/bst20170574
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发表时间：
2018-10-19
影响因子：
3.9
通讯作者：
Jeltsch A
中科院分区：
文献类型：
--
作者：
Gowher H;Jeltsch A
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因子。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位点具有高度偏好，DNMT3A和DNMT3B同样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，我们回顾了最近的观察和新的见解哺乳动物DNMTs（DNA甲基转移酶）的结构和功能，包括DNMT1和DNMT3A的新结构，其机制的数据，通过翻译后修饰的调节和DNMTs在细胞中的功能。此外，我们提出了关于染色质修饰和染色质蛋白质对DNMT的变构调节和靶向的新发现。综合起来，这里总结的最近出版物令人印象深刻地说明了在这一领域正在进行的研究的强度。它们提供了对DNMT关键机械特性的更深入理解，但它们也记录了尚未解决的问题，这些问题需要在未来的研究中解决。
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.