Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
Biochem Soc Trans. 2019 Jun 28;47(3):875-885. doi: 10.1042/BST20180606. Epub 2019 Jun 17.
Ten-eleven translocation (TET) methylcytosine dioxygenases (TET1, TET2, TET3) actively cause demethylation of 5-methylcytosine (5mC) and produce and safeguard hypomethylation at key regulatory regions across the genome. This 5mC erasure is particularly important in pluripotent embryonic stem cells (ESCs) as they need to maintain self-renewal capabilities while retaining the potential to generate different cell types with diverse 5mC patterns. In this review, we discuss the multiple roles of TET proteins in mouse ESCs, and other vertebrate model systems, with a particular focus on TET functions in pluripotency, differentiation, and developmental DNA methylome reprogramming. Furthermore, we elaborate on the recently described non-catalytic roles of TET proteins in diverse biological contexts. Overall, TET proteins are multifunctional regulators that through both their catalytic and non-catalytic roles carry out myriad functions linked to early developmental processes.
十号十一号易位（TET）甲基胞嘧啶双加氧酶（TET1、TET2、TET3）可积极促使 5-甲基胞嘧啶（5mC）去甲基化，并在基因组的关键调控区域产生和维持低甲基化。这种 5mC 的消除在多能胚胎干细胞（ESCs）中尤为重要，因为它们需要在保持自我更新能力的同时，保留生成具有不同 5mC 模式的不同细胞类型的潜力。在这篇综述中，我们讨论了 TET 蛋白在小鼠 ESCs 中的多种作用，以及其他脊椎动物模型系统中的作用，特别关注 TET 蛋白在多能性、分化和发育性 DNA 甲基组重编程中的功能。此外，我们详细阐述了 TET 蛋白在不同生物背景下最近描述的非催化作用。总的来说，TET 蛋白是多功能调节剂，通过其催化和非催化作用，执行与早期发育过程相关的多种功能。
