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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 被引量:5

Mechanisms of TET protein-mediated DNA demethylation and its role in the regulation of mouse development
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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 m C)氧化为5-羟甲基胞嘧啶(5-hydroxymethylcytosine,5 hm C)、5-甲酰基胞嘧啶(5-formylcytosine,5 f C)及5-羧基胞嘧啶(5-carboxylcytosine,5 ca C)。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 (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 TET proteins will open a new field in epigenetic research, and these studies on TET proteins are of great significance to life science research. Here, we review TET proteins from their structure, molecular mechanisms of DNA demethylation and function in the regulation of mouse development, which may provide the basis for under-standing the functions of TET proteins.
出处 《遗传》 CAS CSCD 北大核心 2015年第1期34-40,共7页 Hereditas(Beijing)
基金 内蒙古民族大学博士科研启动基金项目(编号:BS299)资助
关键词 TET蛋白 去甲基化 表观遗传 小鼠发育 TET proteins demethylation epigenetics mouse development
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