Division of Signaling and Gene Expression, La Jolla Institute, La Jolla, CA, United States.
Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.
Front Immunol. 2019 Feb 12;10:210. doi: 10.3389/fimmu.2019.00210. eCollection 2019.
DNA methylation is an abundant and stable epigenetic modification that allows inheritance of information from parental to daughter cells. At active genomic regions, DNA methylation can be reversed by TET (Ten-eleven translocation) enzymes, which are responsible for fine-tuning methylation patterns. TET enzymes oxidize the methyl group of 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC) and other oxidized methylcytosines, facilitating both passive and active demethylation. Increasing evidence has demonstrated the essential functions of TET enzymes in regulating gene expression, promoting cell differentiation, and suppressing tumor formation. In this review, we will focus on recent discoveries of the functions of TET enzymes in the development and function of lymphoid and myeloid cells. How TET activity can be modulated by metabolites, including vitamin C and 2-hydroxyglutarate, and its potential application in shaping the course of immune response will be discussed.
DNA 甲基化是一种丰富且稳定的表观遗传修饰，允许信息从亲代细胞传递到子细胞。在活跃的基因组区域，TET（Ten-eleven translocation）酶可以逆转 DNA 甲基化，这些酶负责精细调节甲基化模式。TET 酶将 5-甲基胞嘧啶（5mC）的甲基基团氧化为 5-羟甲基胞嘧啶（5hmC）和其他氧化的甲基胞嘧啶，促进被动和主动去甲基化。越来越多的证据表明，TET 酶在调节基因表达、促进细胞分化和抑制肿瘤形成方面具有重要功能。在这篇综述中，我们将重点介绍 TET 酶在淋巴和髓样细胞发育和功能中的作用的最新发现。TET 活性如何被代谢物（包括维生素 C 和 2-羟基戊二酸）调节，以及其在塑造免疫反应过程中的潜在应用将被讨论。
