中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
2018国际生命健康产业(上海)展览会暨高峰论坛 第29卷第7期第941-945页一文撤稿声明 2018基因编辑学术研讨会 关于有网站冒充本刊网站的声明
《生命科学》 2017, 29(10): 919-925
TET双加氧酶介导的主动去甲基化分子机制及功能研究
王 超,徐国良*
(中国科学院上海生命科学研究院生物化学与细胞生物学研究所,上海 200031)
摘 要:DNA 甲基化作为一种重要的表观修饰,在基因表达调控及胚胎生长发育等方面起到重要作用。尽管5- 甲基胞嘧啶(5mC) 是一种稳定的共价修饰,但它在生物体内仍处于一个动态变化的过程,也就是说,它可能会通过某种方式发生去甲基化。而TET 蛋白功能的揭示为DNA 主动去甲基化提供了一条途径:TET 双加氧酶可以将5mC 迭代氧化形成5- 羟甲基胞嘧啶(5hmC)、5- 醛基胞嘧啶 (5fC) 和5- 羧基胞嘧啶(5caC),再通过DNA 糖苷酶TDG 介导的碱基切除修复(base excision repair, BER) 途径将5mC 重新变为未修饰的胞嘧啶。随着人们对TET 双加氧酶及主动去甲基化研究的深入,主动去甲基化的生物学功能也被逐渐揭示。现总结了已经揭示的主动去甲基化分子机制和生物学意义,同时,概括了本实验室近些年的研究进展。
 
The mechanism and function of DNA active demethylation mediated by TET dioxygenases
WANG Chao, XU Guo-Liang*
(Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences, Shanghai 200031, China)
Abstract: DNA methylation, as one of the best characterized epigenetic modifications, has its important roles in the regulation of gene expression and embryogenesis. Although 5-methylcytosine (5mC) is a relatively stable modification, it is dynamically altered during embryo development. 5mC may be reversed to its unmodified state. The discovery of Ten-Eleven Translocation (TET) family dioxygenases has provided insights into a pathway of DNA active demethylation: TET enzymes mediate the iterative oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), then 5fC and 5caC are replaced by unmodified cytosine (C) through TDG-mediated base excision repair (BER) pathway. As the research into TET enzymes deepens, a more comprehensive functional assessment of DNA active demethylation has become possible. In this review, we attempt to summarize the recent advances, and share some of our new findings made over the past few years.
 
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