Hydroxymethyl cytosine marks in the human mitochondrial genome are dynamic in nature
Hydroxymethyl cytosine marks in the human mitochondrial genome are dynamic in nature
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DOI：
10.1016/j.mito.2016.01.003
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发表时间：
2016-03-01
期刊：
影响因子：
4.4
通讯作者：
Scaria, Vinod
中科院分区：
文献类型：
--
作者：
Ghosh, Sourav;Sengupta, Shantanu;Scaria, Vinod
除DNA甲基化外，羟甲基化作为一种重要的表观遗传标记已得到越来越多的研究。5-羟甲基胞嘧啶，虽然最初被认为是去甲基化的中间产物，但最近的研究表明，这是一个高度调控的过程，由TET家族酶调节。最近的全基因组研究表明，羟甲基胞嘧啶标记与转录和胚胎发育等重要生物学过程的调控密切相关。众所周知，异常的羟甲基化标记与癌症等疾病有关。羟基甲基胞嘧啶在线粒体基因组中的存在早前已被提出，尽管基因组尺度的图谱尚未被绘制出来。在本研究中，我们利用23个不同的公开数据集绘制和分析了线粒体基因组中的羟甲基胞嘧啶标记。我们通过检查先前标注为羟甲基胞嘧啶的基因组区域子集的一致性来交叉验证我们的数据，并显示出良好的一致性。我们观察到线粒体基因组中羟甲基化标记的动态分布。与甲基胞嘧啶标记不同，羟甲基胞嘧啶标记的特点是在所考虑的样品中缺乏保守性，尽管相似的细胞类型共享这种模式。此外，我们还观察到羟甲基化标记富集在GSS（基因起始位点）上游区域和与核基因相似的基因体中。据我们所知，这是人类线粒体基因组中第一个基因组尺度的羟甲基胞嘧啶图谱。(C) 2016 Elsevier B.V.与线粒体研究学会。版权所有。
Apart from DNA methylation, hydroxymethylation has increasingly been studied as an important epigenetic mark. 5-hydroxymethylcytosines, though initially were thought to be an intermediary product of demethylation, recent studies suggest this to be a highly regulated process and modulated by the TET family of enzymes. Recent genome wide studies have shown that hydroxymethylcytosine marks are closely associated with the regulation of important biological processes like transcription and embryonic development. It is also known that aberrant hydroxymethylation marks have been associated with diseases like cancer. The presence of hydroxymethylcytosines in the mitochondrial genome has been earlier suggested, though the genome-scale map has not been laid out. In this present study, we have mapped and analyzed the hydroxymethylcytosine marks in the mitochondrial genome using 23 different publicly available datasets. We cross validated our data by checking for consistency across a subset of genomic regions previously annotated to hydroxymethylcytosines and show good consistency. We observe a dynamic distribution of hydroxymethylation marks in the mitochondrial genome. Unlike the methylcytosine marks, hydroxymethylcytosine marks are characterized by the lack of conservation across the samples considered, though similar cell types shared the pattern. We additionally observed that the hydroxymethylation marks are enriched in the upstream of GSS (gene start site) regions and in gene body as similar as nuclear genes. To the best of our knowledge, this is the first genome-scale map of hydroxymethyl cytosines in the human mitochondrial genome. (C) 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.