In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine (C) through TET dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution or thymine DNA glycosylase (TDG)-dependent base excision repair. In the past few years, biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation. Additionally, many regulatory mechanisms of this process have been identified. Technological advances in mapping and tracing the oxidized forms of 5mC allow further dissection of their functions. Furthermore, the biological functions of active DNA demethylation in various biological contexts have also been revealed. In this Review, we summarize the recent advances and highlight key unanswered questions.

中文翻译：

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TET介导的活性DNA去甲基化：机理，功能及其他

在哺乳动物中，可以通过TET双加氧酶介导的5mC氧化成5-羟甲基胞嘧啶（5hmC），5-甲酰基胞嘧啶（5fC）和5-甲基苯丙氨酸，将5-甲基胞嘧啶（5mC）形式的DNA甲基化主动逆转为未修饰的胞嘧啶（C）。羧基胞嘧啶（5caC），然后进行复制依赖性稀释或胸腺嘧啶DNA糖基化酶（TDG）依赖性碱基切除修复。在过去的几年中，生化和结构研究揭示了有关TET和TDG如何介导活性DNA去甲基化的机理见解。另外，已经确定了该过程的许多调节机制。映射和追踪5mC氧化形式的技术进步可以进一步剖析其功能。此外，还已经揭示了在各种生物学背景下活性DNA去甲基化的生物学功能。在这篇评论中，