TET proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidation products in DNA. The oxidized methylcytosines (oxi-mCs) facilitate DNA demethylation and are also novel epigenetic marks. TET loss-of-function is strongly associated with cancer; TET2 loss-of-function mutations are frequently observed in hematological malignancies that are resistant to conventional therapies. Importantly, TET proteins govern cell fate decisions during development of various cell types by activating a cell-specific gene expression program. In this review, we seek to provide a conceptual framework of the mechanisms that fine tune TET activity. Then, we specifically focus on the multifaceted roles of TET proteins in regulating gene expression in immune cell development, function, and disease.

TET蛋白将5-甲基胞嘧啶（5mC）氧化为5-羟甲基胞嘧啶（5hmC），并进一步氧化DNA中的氧化产物。氧化的甲基胞嘧啶（oxi-mCs）促进DNA脱甲基化，并且也是新的表观遗传标记。TET功能丧失与癌症密切相关；TET2在对常规疗法有抵抗力的血液系统恶性肿瘤中经常观察到功能丧失突变。重要的是，TET蛋白通过激活细胞特异性基因表达程序来控制各种细胞类型发育过程中的细胞命运决定。在这篇综述中，我们力求提供一个微调TET活动机制的概念框架。然后，我们专门关注TET蛋白在调节免疫细胞发育，功能和疾病中的基因表达中的多方面作用。