TET蛋白的去甲基化机制及在调控小鼠发育过程中的作用.pdfVIP

Hereditas (Beijing) 2015 年 1 月, 37(1): 34 ―40 综 述 TET 蛋白的去甲基化机制及其在调控小鼠发育过程中 的作用 贾振伟，高树新，张永春，张显华 内蒙古民族大学动物科技学院，黄牛遗传繁育研究所，通辽 028043 摘要:TET(Ten-eleven translocation)蛋白家族共有3 个成员，分别为TET1 、TET2 和TET3 ，均属于α-酮戊二酸 (α-KG) 和 Fe2+ 依赖的双加氧酶，可以将 5- 甲基胞嘧啶(5-methylcytosine, 5 mC) 氧化为 5- 羟甲基胞嘧啶 (5-hydroxymethylcytosine, 5 hmC) 、 5- 甲酰基胞嘧啶(5-formylcytosine, 5 fC) 及 5- 羧基胞嘧啶 (5-carboxylcytosine, 5 caC)。研究表明，TET 蛋白通过不同机制以主动或被动的方式调控DNA 去甲基化，且去 甲基化的活性可能受其他因子的调控。TET 蛋白广泛参与哺乳动物发育过程的调节，其中在原始生殖细胞的形 成、胚胎发育、干细胞多能性及神经和脑发育等方面发挥了重要作用。TET 蛋白生物功能的发现为表观遗传学 研究开辟了全新的研究领域，而且相关研究结果对拓展生命科学研究具有重要意义。文章综述了 TET 蛋白家 族的结构、去甲基化分子机制及在小鼠发育过程中的作用，为深入了解 TET 蛋白的功能提供理论基础。 TET 蛋白；去甲基化；表观遗传；小鼠发育 关键词: Mechanisms of TET protein-mediated DNA demethylation and its role in the regulation of mouse development Zhenwei Jia, Shuxin Gao, Yongchun Zhang, Xianhua Zhang Institute of Yellow Cattle Genetics-Breeding and Reproduction, College of Animal Science and Technology, Inner Mongolia Unive r- sity for the Nationalities, Tongliao 028000, China Abstract: TET (ten-eleven translocation) protein family includes three members TET1, TET2 and TET3, which be- long to alpha-ketoglutaric acid ( α-KG )- and Fe2+-dependent dioxygenase superfamily, and have the capacity to con- vert 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5 fC) and 5-carboxylcytosine (5 caC). At present, growing lines of evidence indicate that TET proteins are involved in the control of active or pas- sive DNA demethylation via different mechanisms; moreover, their activities may be regulated by some cellular fac- tors . TET proteins play vital roles in modulating mammal development, including primordial germ cell formation, embryonic development, stem cells pluripotency, nerve and brain development, etc. The identification of biological roles of