哺乳动物DNA甲基化修饰的动态调控机制

Dynamic regulation of mammalian DNA methylation

DNA甲基化是最主要的表观遗传修饰之一,主要发生在胞嘧啶第五位碳原子上,称为5-甲基胞嘧啶。哺乳动物DNA甲基化由从头DNA甲基转移酶DNMT3A/3B在胚胎发育早期建立。细胞分裂过程中甲基化模式的维持由DNA甲基转移酶DNMT1实现。TET家族蛋白氧化5-甲基胞嘧啶成为5-羟甲基胞嘧啶、5-醛基胞嘧啶和5-羧基胞嘧啶,从而起始DNA的去甲基化过程。这些DNA甲基化修饰酶精确调节DNA甲基化的动态过程,在整个生命发育过程中发挥重要作用,其失调也与多种疾病发生密切相关。本文对近年来DNA甲基化修饰酶的结构与功能研究进行讨论。

DNA methylation is one of the most important epigenetic modification, which mainly occurs at the carbon 5 position of cytosine （5-methylcytosine, 5mC） in a context of cytosine-guanine （CpG） diimcleo- tide. Mammalian DNA methylation is established by de novo DNA methyltransferases DNMT3A/3B in em- bryonic development and the patterns of methylation are propagated to daughter cells by maintenance DNA methyltransferases DNMT1 during replication. TET proteins oxidize 5mC into 5-hydroxymethylcytosine （ShmC）, 5-formylcytosine （SfC）, and 5-carboxylcytosine （ScaC）, and thus initiate DNA demethylation. These enzymes play important roles in various biological processes during development and their dysregulation are involved in many pathological processes. Here, we summarized structural and functional studies of these en- zymes.