TET蛋白:一个新的DNA修饰酶家族  

TET Proteins:A New Family of DNA Modifying Enzymes

作　　者：郭晓强[1,2] 王越甲[1] 郭振清[3] 常彦忠[1] 段相林[1] 

机构地区：[1]河北师范大学生命科学学院铁代谢分子生物学研究室,河北石家庄050016 [2]解放军白求恩军医学院生物化学教研室,河北石家庄050081 [3]河北科技师范学院生命科学系,河北秦皇岛066600

出　　处：《中国生物化学与分子生物学报》2011年第12期1101-1106,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.30870265);河北省自然基金项目(No.C2010000410)~~

摘　　要：DNA的胞嘧啶(C)5-甲基化是一种重要的表观修饰,它参与基因调节、基因组印记、X-染色体失活、重复序列抑制和癌症发生等过程.5-甲基胞嘧啶(5mC)可被TET(ten-eleven translocation)蛋白家族进一步转化为5-羟甲基胞嘧啶(5hmC),该过程是DNA去甲基化的1个必要阶段.5hmC可在活性转录基因起始位点和Polycomb抑制基因启动子延伸区域富集.TET蛋白包括3个成员TET1、TET2和TET3,均属于α-酮戊二酸和Fe2+依赖的双加氧酶,其催化涉及氧化过程.小鼠Tet1在胚胎干细胞发育中拥有双重作用,即促进全能因子的转录,又参与发育调节因子的抑制.人TET蛋白的破坏与造血系统肿瘤相关,如在骨髓增生性疾病/肿瘤存在频繁的TET2基因突变.TET蛋白和5hmC的研究为DNA甲基化/去甲基化及其生物学功能提供了新的视点.Methylation at the 5 position of cytosine（C） in DNA is an important epigenetic modification involved in gene regulation,genomic imprinting,X-chromosome inactivation,suppression of repetitive elements,and carcinogenesis.The 5-methylcytosine（5mC） can be further converted to 5-hydroxymethylcytosine（5hmC） by TET（ten-eleven translocation） proteins family,which is essential for DNA demethylation.5hmC is enriched at both the start sites of actively transcribed genes and extended promoter regions of Polycomb-repressed genes.TET proteins include three members TET1,TET2 and TET3,and belong to alpha-ketoglutaric acid（α-KG）-and Fe2＋-dependent dioxygenases in which catalysis is a oxidative process.Mouse Tet1 has a dual function in promoting transcription of pluripotency factors and participating in the repression of developmental regulators in embryonic stem cells.The disruptions of human TET proteins are associated with hematologic malignancies,such as frequently mutation of TET2 in myeloproliferative disorders/ neoplasms.These studies on TET proteins and 5hmC will provide new perspective for DNA methylation /demethylation and their biological function.

关 键 词：TET蛋白 DNA去甲基化 5-甲基胞嘧啶 5-羟甲基胞嘧啶 转录调节 

分 类 号：Q55[生物学—生物化学] Q71