DNA主动去甲基化酶研究进展及药物开发  

DNA demethylases: a new direction for drug development

作　　者：段菊[1] 凌霜[1] 甘我挺[1] 孙丽[1] 许锦文[1] 

机构地区：[1]上海中医药大学穆拉德中药现代化研究中心,上海201203

出　　处：《中国药理学通报》2013年第10期1345-1349,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81274130);国家自然科学基金-青年科学基金资助项目(No 81102532);教育部高等学校博士学科点专项科研基金(博导类)(No20113107110006);上海市教委085项目高等教育内涵建设基金(No 085ZY1202);上海市教委科研创新项目(自然科学类)重点项目(No 10ZZ75;12ZZ122)

摘　　要：DNA甲基化是一种相对稳定且可遗传的表观遗传修饰,大量研究表明,DNA甲基化影响DNA的许多重要生物学功能,包括基因印迹、X染色体的失活、基因组稳定性的维持、转座子及逆转录转座子的沉默及组织特异性基因的沉默等,也与癌症、心血管疾病、代谢性疾病、炎症等疾病的发生发展过程相关,是当代表观遗传学研究比较清晰的部分。而作为其表观遗传调控平衡的DNA主动去甲基化现象是近几年研究开始探索的热点之一,DNA去甲基化能诱导基因的重新活化及功能表达,动植物细胞中均发现DNA主动去甲基化现象,目前其相关机制研究已获得不小进展。本文就目前DNA主动去甲基化及相关酶类的累积报道和文献进行综述,对DNA去甲基化调节机制进一步理解以期拓宽对表观遗传调控的认识,为开发药物介导DNA去甲基化过程从而参与治疗疾病提供了新的思考方向。DNA methylation is a relatively stable and heritable epigenetie modification. A large number of studies have shown that DNA methylation affects many important biological functions of DNA, including gene imprinting, X chromosome inactivation, genome stability maintenance, transposon and retrotransposon si- lencing and tissue-specific gene silencing. It is also associatedwith the occurrence and development of cancer, cardiovascular diseases, metabolic diseases, inflammatory diseases. While as the balance epigenetic regulation, DNA active dcmethylation phenomenon began to be one of the hot spots. DNA methylation phenomenon is found in animal and plant cells, and the studies of its mechanisms have shown large progress. This paper reviews the cumulative report and literature about DNA active demetby- lase, gives a further understanding of the regulatory mechanism of DNA demethylation to broaden our understanding of epigenetic regulation, and to provide a new direction of thinking for the development of drug-mediated DNA demethylation process to par-tieipate in the treatment of diseases.

关 键 词：表观遗传学 DNA去甲基化 DNA主动去甲基化酶 衰老 TET DNA去甲基化药物开发 

分 类 号：R-05[医药卫生] R339.38