双加氧酶TET1表观遗传调控作用研究进展

Advances in epigenetic regulation of the dioxygenase TET1

摘要:

Ten-eleven translocation 1 (TET1)蛋白是一种α-酮戊二酸(alpha-ketoglutaric acid, α-KG)和Fe²⁺依赖性的双加氧酶，通过将5-甲基胞嘧啶(5-methyl-cytosine, 5-mC)羟化成5-羟甲基胞嘧啶(5-hydroxymethyl-cytosine, 5-hmC)，完成DNA的主动去甲基化修饰过程。TET1参与维持基因组甲基化稳态并实现表观遗传调控，异常表达的TET1与5-mC氧化衍生物已经成为各种生物学和病理学过程中的潜在标志物，尤其在胚胎发育和恶性肿瘤等领域中逐渐成为研究热点。本文介绍了双加氧酶TET1的结构和去甲基化作用的机制，综述了其在胚胎发育、免疫应答、干细胞调控、癌症发展和神经系统发育等过程中发挥表观遗传调控作用的研究现状，并简述了其上游调控机制，为相关领域的深入研究提供了新的思路。

Abstract:

Ten-eleven translocation 1 (TET1) protein is an alpha-ketoglutaric acid (α-KG) and Fe²⁺-dependent dioxygenase. It plays a role in the active demethylation of DNA by hydroxylation of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC). Ten-eleven translocation 1 (TET1) protein is involved in maintaining genome methylation homeostasis and epigenetic regulation. Abnormally expressed TET1 and 5-mC oxidative derivatives have become potential markers in various biological and pathological processes and a research focus in the fields of embryonic development and malignant tumors. This paper introduces the structure and demethylation mechanism of TET1, reviews the research status of epigenetic regulation by TET1 in embryonic development, immune responses, stem cell regulation, cancer progression, and nervous system development, and briefs the upstream regulatory mechanism of TET1, hoping to provide new inspirations for further research in related fields.