Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues - Implications for epigenetic reprogramming
Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues - Implications for epigenetic reprogramming
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DOI：
10.1074/jbc.m407695200
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发表时间：
2004-12-10
影响因子：
4.8
通讯作者：
Petersen-Mahrt, SK
中科院分区：
文献类型：
--
作者：
Morgan, HD;Dean, W;Petersen-Mahrt, SK
Aid/Apobec家族的DNA脱氨酶将胞嘧啶转化为尿嘧啶，并在获得性和先天性免疫中发挥关键作用。CpG二核苷酸中胞嘧啶甲基化的表观遗传修饰也具有致突变性，但认为这是通过自发脱氨基作用发生的。在这里，我们表明，援助和Apobec 1是5-甲基胞嘧啶脱氨酶，导致在胸腺嘧啶基地相反的鸟嘌呤。因此，它们的作用可以导致甲基化DNA中的C -> T转换突变，或者与T：G错配的修复一起导致去甲基化。Aid和Apobec 1基因位于包括Nanog和Stella在内的多能性基因簇中，并在卵母细胞、胚胎生殖细胞和胚胎干细胞中与这些基因共表达。这些结果表明，Aid和它的一些家族成员可能在表观遗传重编程和细胞可塑性中发挥作用。CpG二核苷酸的转换是人类遗传性疾病中最常见的突变，APC肿瘤抑制基因中CpG转换的序列背景分析表明，DNA脱氨酶可能在肿瘤病因学中发挥重要作用。
DNA deaminases of the Aid/Apobec family convert cytosine into uracil and play key roles in acquired and innate immunity. The epigenetic modification by methylation of cytosine in CpG dinucleotides is also mutagenic, but this is thought to occur by spontaneous deamination. Here we show that Aid and Apobec1 are 5-methylcytosine deaminases resulting in a thymine base opposite a guanine. Their action can thus lead to C --> T transition mutations in methylated DNA, or in conjunction with repair of the T:G mismatch, to demethylation. The Aid and Apobec1 genes are located in a cluster of pluripotency genes including Nanog and Stella and are co-expressed with these genes in oocytes, embryonic germ cells, and embryonic stem cells. These results suggest that Aid and perhaps some of its family members may have roles in epigenetic reprogramming and cell plasticity. Transition in CpG dinucleotides is the most frequent mutation in human genetic diseases, and sequence context analysis of CpG transitions in the APC tumor suppressor gene suggests that DNA deaminases may play a significant role in tumor etiology.