《生命科学》 2017, 29(10): 926-933
摘 要：摘 要：发生在DNA 胞嘧啶上的甲基化(5mC) 是哺乳动物细胞基因组上最主要的DNA 修饰形式，其形成的碳碳键具有较高键能，不易被破坏。TET 家族蛋白可以催化5mC 逐渐氧化成羟甲基胞嘧啶(5hmC)、醛基胞嘧啶(5fC) 和羧基胞嘧啶(5caC)，再通过细胞分裂过程中DNA 复制，或者利用碱基切除修复途径，最终实现DNA 去甲基化。过去几年表观基因组学和结构生物学的研究都表明，在不同细胞、不同的基因组位点，5mC 的氧化反应受到严格的调控，主要表现在两个方面：5mC 氧化反应发生的基因组范围和5mC逐步氧化反应的进行程度。以国家自然科学基金委重大研究计划“细胞编程和重编程的表观遗传机制”为依托，朱冰实验室发现了胚胎干细胞的多能性转录因子SALL4A 与TET 家族蛋白共同调节远端调控区域5mC 的氧化过程。首先，将介绍5mC 的不同氧化产物在小鼠基因组上的分布和动态变化，进而讨论TET
家族蛋白催化5mC 氧化反应的调控机制，最后，探讨5mC 氧化参与调节基因组转录的可能的生物学功能。
Abstract: Abstract: 5-methylcytosine is the most abundant modified nucleotide in mammalian genome， which is hard to remove from the genome due to the carbon-carbon bond between the methyl group and cytosine. TET family proteins successively catalyze 5mC to oxidized forms including 5-hydroxymethylcytosine (5hmC)， 5-formylcytosine (5fC)， and 5-carboxylcytosine (5caC)， which may result in eventual demethylation through passive dilution during mitosis or with the help of thymine DNA glycosylase (TDG) and the base excision repair machinery. Recent genomic mapping and structural studies have revealed that 5mC oxidation in the genome is strictly regulated at multiple layers. In this review， we first describe the distribution and dynamics of different 5mC oxidative products in mouse genomes. Then we summarize current knowledge on how the oxidation reaction is controlled. Finally， we discuss the possible role of TET-mediated DNA oxidation in transcription regulation.
