Ten-eleven translocation (TET) proteins are iron-dependent and α-ketoglutarate-dependent dioxygenases that sequentially oxidize the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). All three epigenetic modifications are intermediates in DNA demethylation. TET proteins are recruited by transcription factors and by RNA polymerase II to modify 5mC at enhancers and gene bodies, thereby regulating gene expression during development, cell lineage specification, and cell activation. It is not yet clear, however, how the established biochemical activities of TET enzymes in oxidizing 5mC and mediating DNA demethylation relate to the known association of TET deficiency with inflammation, clonal hematopoiesis, and cancer. There are hints that the ability of TET deficiency to promote cell proliferation in a signal-dependent manner may be harnessed for cancer immunotherapy. In this review, we draw upon recent findings in cells of the immune system to illustrate established as well as emerging ideas of how TET proteins influence cellular function.Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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免疫系统中的 TET 酶：从 DNA 去甲基化到免疫治疗、炎症和癌症

十十一易位 (TET) 蛋白是铁依赖性和 α-酮戊二酸依赖性双加氧酶，可依次将 5-甲基胞嘧啶 (5mC) 的甲基氧化为 5-羟甲基胞嘧啶 (5hmC)、5-甲酰基胞嘧啶 (5fC) 和 5-羧基胞嘧啶（5caC）。所有三种表观遗传修饰都是 DNA 去甲基化的中间产物。 TET 蛋白由转录因子和 RNA 聚合酶 II 招募来修饰增强子和基因体的 5mC，从而在发育、细胞谱系规范和细胞激活过程中调节基因表达。然而，目前尚不清楚 TET 酶氧化 5mC 和介导 DNA 去甲基化的生化活性如何与已知的 TET 缺乏与炎症、克隆造血和癌症的关联相关。有迹象表明，TET 缺陷以信号依赖性方式促进细胞增殖的能力可用于癌症免疫治疗。在这篇综述中，我们利用免疫系统细胞的最新发现来说明 TET 蛋白如何影响细胞功能的既定观点和新兴观点。《免疫学年度评论》第 42 卷的预计最终在线出版日期为 2024 年 4 月。有关修订后的估计，请参阅 http://www.annualreviews.org/page/journal/pubdates。