1] Department of Medicine, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA. [2] Department of Biochemistry and Biophysics, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Nature. 2013 Oct 24;502(7472):472-9. doi: 10.1038/nature12750.
DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.
DNA 甲基化对基因组稳定性、转录和发育有深远影响。尽管催化 DNA 甲基化的酶已得到很好的描述，但参与甲基去除的酶一直难以捉摸，直到最近。一项具有变革性的发现表明，ten-eleven translocation（TET）家族酶可以氧化 5-甲基胞嘧啶，这极大地促进了我们对 DNA 去甲基化的理解。5-羟甲基胞嘧啶是去甲基化的关键枢纽，它可以通过 DNA 复制被动耗尽，也可以通过反复氧化和胸腺嘧啶 DNA 糖基化酶（TDG）介导的碱基切除修复主动恢复为胞嘧啶。甲基化、氧化和修复现在为动态胞嘧啶修饰的完整循环提供了一个模型，越来越多的证据表明它在涉及主动去甲基化的已知生物学过程中具有重要意义。
