真核生物基因组DNA甲基化和去甲基化分析  

Sensitive analysis of DNA methylation and demethylation intermediates for eukaryotes

作　　者：刘保东 汪海林[1,2] LIU Bao-Dong1,WANG Hai-Lin1,2(1 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; 2 University of Chinese Academy of Sciences, Beijing 100049, Chin)

机构地区：[1]中国科学院生态环境研究中心环境化学与生态毒理学国家重点实验室,北京100085 [2]中国科学院大学,北京100049

出　　处：《生命科学》2018年第4期374-382,共9页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(21435008;9174321)

摘　　要：DNA甲基化是真核生物的重要表观遗传修饰,如胞嘧啶C^5位甲基化5-甲基胞嘧啶(5mC)和腺嘌呤N^6位甲基化6-甲基腺嘌呤(6mA)。DNA 5mC可经Tet双加氧酶催化氧化形成5-羟甲基胞嘧啶(5hmC)、5-醛甲基胞嘧啶(5fC)和5-羧基胞嘧啶(5caC)。这些氧化产物不仅是去甲基化过程的中间体,而且也可能存在各自特有的表观调控功能。其中,5hmC异常可能和癌症相关,有可能成为疾病诊断的生物标志物。发展可靠、高灵敏和抗干扰能力强的DNA甲基化和去甲基化检测技术和方法至关重要,有助于理解甲基化和去甲基化的分子机制以及提高肿瘤的诊断水平。现针对DNA甲基化和去甲基化检测技术进行简要介绍。Eukaryotic DNA methylations, including methylation of C^5 position of cytosine 5-methylcytosine（5 m C） and N^6 position of adenine（6-methyladenine, 6 m A）, are critical and important epigenetic markers. DNA 5 m C can be oxidized to form three intermediates, 5-hydroxymethylcytosine（5 hm C）, 5-formylcytosine（5 f C）, 5-carboxylcytosine（5 ca C）, as catalized by Tet family dioxygenases. In addition to being as demethylation intermediates, 5 hm C content is negatively correlated with tumor occurrence, and thus is a potential biomarker indicating occurrence and development of tumors. To understand these events and underlying mechanisms, it is essential to develop reliable, sensitive and interference-free methods for detection of DNA methylation and demethylation. Here we briefly review and discuss analytical and sequencing technologies for detection of epigenetic modifications involved in DNA methylation and demethylation.

关 键 词：DNA甲基化 DNA去甲基化 检测方法 5mC 6mA 5hmC 5fC 5caC 5hmU 

分 类 号：Q523.03[生物学—生物化学] Q71