DNA methylation: TET proteins-guardians of CpG islands?

被引：226
作者：
Williams, Kristine [1 ,2 ]
Christensen, Jesper [1 ,2 ]
Helin, Kristian [1 ,2 ]
机构：
[1] Univ Copenhagen, BRIC, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark
[2] Univ Copenhagen, Ctr Epigenet, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark
来源：
EMBO REPORTS | 2012年 / 13卷 / 01期
基金：
英国医学研究理事会; 新加坡国家研究基金会;
关键词：
DNA methylation; 5-hydroxymethylcytosine; TET proteins; stem cells; cancer; HEMATOPOIETIC STEM-CELLS; DE-NOVO METHYLATION; SELF-RENEWAL; 5-HYDROXYMETHYLCYTOSINE; MOUSE; 5-METHYLCYTOSINE; MUTATIONS; 5-FORMYLCYTOSINE; HYDROXYLATION; TRANSCRIPTION;
D O I：
10.1038/embor.2011.233
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
DNA methylation is involved in key cellular processes, including X-chromosome inactivation, imprinting and transcriptional silencing of specific genes and repetitive elements. DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. The recent discovery that the three members of the TET protein family can convert 5-methyl-cytosine (5mC) into 5-hydroxymethylcytosine (5hmC) has provided a potential mechanism leading to DNA demethylation. Moreover, the demonstration that TET2 is frequently mutated in haematopoietic tumours suggests that the TET proteins are important regulators of cellular identity. Here, we review the current knowledge regarding the function of the TET proteins, and discuss various mechanisms by which they contribute to transcriptional control. We propose that the TET proteins have an important role in regulating DNA methylation fidelity, and that their inactivation contributes to the DNA hypermethylation phenotype often observed in cancer.
引用
收藏
页码：28 / 35
页数：8
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