Ko Myunggon, An Jungeun, Rao Anjana
School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulju-gun, Ulsan 689-798, Republic of Korea.
Center for Genomic Integrity, Institute for Basic Science (IBS), UNIST-gil 50, Ulju-gun, Ulsan 689-798, Republic of Korea.
Curr Opin Cell Biol. 2015 Dec;37:91-101. doi: 10.1016/j.ceb.2015.10.009. Epub 2015 Nov 18.
Maintenance of the balance of DNA methylation and demethylation is fundamental for normal cellular development and function. Members of the Ten-Eleven-Translocation (TET) family proteins are Fe(II)-dependent and 2-oxoglutarate-dependent dioxygenases that catalyze sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and subsequent oxidized derivatives in DNA. In addition to their roles as intermediates in DNA demethylation, these oxidized methylcytosines are novel epigenetic modifications of DNA. DNA methylation and hydroxymethylation profiles are markedly disrupted in a wide range of cancers but how these changes are related to the pathogenesis of cancers is still ambiguous. In this review, we discuss the current understanding of TET protein functions in normal and malignant hematopoietic development and the ongoing questions to be resolved.
维持DNA甲基化和去甲基化的平衡是正常细胞发育和功能的基础。TET（Ten-Eleven-Translocation）家族蛋白成员是依赖于Fe(II)和2-氧戊二酸的双加氧酶，可催化DNA中5-甲基胞嘧啶（5mC）依次氧化为5-羟甲基胞嘧啶（5hmC）及其后续氧化衍生物。除了作为DNA去甲基化的中间体发挥作用外，这些氧化的甲基胞嘧啶还是DNA的新型表观遗传修饰。在多种癌症中，DNA甲基化和羟甲基化谱均受到明显破坏，但这些变化与癌症发病机制之间的关系仍不明确。在本综述中，我们讨论了目前对TET蛋白在正常和恶性造血发育中的功能的理解以及有待解决的问题。
