DNA羟甲基化酶TET2突变对其功能的影响

Mutations of TET2,DNA hydroxymethylase,affect its function

DNA羟甲基化是继DNA甲基化之后发现的又一重要的表观遗传修饰,在基因的表达调控、染色体重塑等方面有着重要功能。TET2(ten-eleven-translocation 2,TET2)基因作为调控DNA羟甲基化形成的TET家族蛋白的成员之一,能够催化5甲基胞嘧啶(5-methyl-cytosine,5m C)形成5羟甲基胞嘧啶(5-hydroxymethyl-cytosine,5hm C),在表观遗传学中具有重要的地位。近年来,在骨髓增生性肿瘤(myeloproliferative neoplasms,MPN)、系统性肥大细胞增生症(systemic mastocytosis,SM)、慢性骨髓单核细胞性白血病(chronic myelomonocytic leukemia,CMML)和骨髓增生异常综合征(myelodysplastic syndrome,MDS)等疾病中均发现了TET2的突变,并影响了5m C和5hm C含量的变化。对TET2突变的研究仍是一个很新颖的课题,TET2在不同疾病中突变的位置和类型以及对其功能的影响尚处于探索研究之中。本文对各类疾病中发现的TET2突变及其功能的影响进行了综述,深入阐述了TET2的突变对拓展DNA去甲基化和寻找疾病新靶标具有的潜在应用价值。

DNA hydroxymethylation is another great discovery of epigenetic modification after DNA methylation which takes an important role in the regulation of gene expression, chromosome remodeling and so on. TET2（Ten-Eleven-Translocation 2）, a member of theTET family, which regulate the formation of DNA hy- droxymethylation, could catalyze 5mC（5-methyl-cytosine） into 5hmC（5-hydroxymethyl-cytosine）, and have a vital role in epigenetics. Recently, TET2 mutations were found in many diseases, such as MPN（myeloprolifer- ative neoplasms）, SM（systemic mastocytosis）, CMML（chronic myelomonocytic leukemia）, MDS（myelodys- plastic syndrome） and so on. TET2 mutations changing the level of 5mC and 5hmC. TET2 mutations is a new topic, the position and type of TET2 mutations and how these mutations affect the function of TET2 are still need to be studied. In this review, we have summarized the TET2 mutations occurred in the known diseases and made in-depth discussion the potential application value of TET2 mutations in DNA demethylation pathy- way and searching new therapeutic target of diseases.