Lazarenkov Aleksey, Sardina José Luis
Epigenetic Control of Haematopoiesis Group, Josep Carreras Leukaemia Research Institute, 08916 Badalona, Spain.
Cancers (Basel). 2022 Feb 6;14(3):830. doi: 10.3390/cancers14030830.
Cytosine methylation (5mC) of CpG is the major epigenetic modification of mammalian DNA, playing essential roles during development and cancer. Although DNA methylation is generally associated with transcriptional repression, its role in gene regulation during cell fate decisions remains poorly understood. DNA demethylation can be either passive or active when initiated by TET dioxygenases. During active demethylation, transcription factors (TFs) recruit TET enzymes (TET1, 2, and 3) to specific gene regulatory regions to first catalyze the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and subsequently to higher oxidized cytosine derivatives. Only is frequently mutated in the hematopoietic system from the three TET family members. These mutations initially lead to the hematopoietic stem cells (HSCs) compartment expansion, eventually evolving to give rise to a wide range of blood malignancies. This review focuses on recent advances in characterizing the main -mediated molecular mechanisms that activate aberrant transcriptional programs in blood cancer onset and development. In addition, we discuss some of the key outstanding questions in the field.
CpG 位点的胞嘧啶甲基化（5mC）是哺乳动物 DNA 的主要表观遗传修饰，在发育和癌症过程中发挥着重要作用。虽然 DNA 甲基化通常与转录抑制相关，但其在细胞命运决定过程中基因调控的作用仍知之甚少。当由 TET 双加氧酶启动时，DNA 去甲基化可以是被动的或主动的。在主动去甲基化过程中，转录因子（TFs）将 TET 酶（TET1、2 和 3）招募到特定的基因调控区域，首先催化 5mC 氧化为 5-羟甲基胞嘧啶（5hmC），随后氧化为更高氧化态的胞嘧啶衍生物。在三个 TET 家族成员中，只有 在造血系统中经常发生突变。这些突变最初导致造血干细胞（HSCs） compartment 扩张，最终演变为引发多种血液恶性肿瘤。本综述重点关注在表征主要 -介导的激活血液癌症发生和发展中异常转录程序的分子机制方面的最新进展。此外，我们还讨论了该领域一些关键的未解决问题。
你提供的原文中存在一些不完整的表述（如“Only is frequently mutated”），可能会影响准确理解，以上译文是基于现有内容尽量完整翻译的。
