Dnmt2-dependent methylomes lack defined DNA methylation patterns
Dnmt2-dependent methylomes lack defined DNA methylation patterns
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DOI：
10.1073/pnas.1306723110
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发表时间：
2013-05-21
影响因子：
11.1
通讯作者：
Lyko, Frank
中科院分区：
文献类型：
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作者：
Raddatz, Guenter;Guzzardo, Paloma M.;Lyko, Frank
一些生物保留了甲基转移酶2（Dnmt2）作为它们唯一的DNA甲基转移酶候选基因。然而，关于dnmt2依赖的甲基化模式的信息仅限于少数孤立的位点，并且结果一直存在争议。此外，最近的研究表明，Dnmt2作为tRNA甲基转移酶起作用，这提出了只有Dnmt2的基因组可能未甲基化的可能性。我们现在已经使用全基因组亚硫酸盐测序在单碱基分辨率下分析只有dnmt2的生物体的甲基组。我们的研究结果表明，曼氏血吸虫和黑腹果蝇的基因组缺乏可检测的DNA甲基化模式。残留的未转化胞嘧啶残基与亚硫酸盐脱氨产物有许多相同的属性，并且在dnmt2缺陷的果蝇中观察到相当的水平。此外，基因修饰的仅dnmt2小鼠胚胎干细胞失去了在野生型细胞中发现的DNA甲基化模式。因此，我们的研究结果揭示了动物甲基组之间的根本差异，并表明DNA甲基化对于相当数量的真核生物是必不可少的。
Several organisms have retained methyltransferase 2(Dnmt2) as their only candidate DNA methyltransferase gene. However, information about Dnmt2-dependent methylation patterns has been limited to a few isolated loci and the results have been discussed controversially. In addition, recent studies have shown that Dnmt2 functions as a tRNA methyltransferase, which raised the possibility that Dnmt2-only genomes might be unmethylated. We have now used whole-genome bisulfite sequencing to analyze the methylomes of Dnmt2-only organisms at single-base resolution. Our results show that the genomes of Schistosoma mansoni and Drosophila melanogaster lack detectable DNA methylation patterns. Residual unconverted cytosine residues shared many attributes with bisulfite deamination artifacts and were observed at comparable levels in Dnmt2-deficient flies. Furthermore, genetically modified Dnmt2-only mouse embryonic stem cells lost the DNA methylation patterns found in wild-type cells. Our results thus uncover fundamental differences among animal methylomes and suggest that DNA methylation is dispensable for a considerable number of eukaryotic organisms.