Human DNA methylomes at base resolution show widespread epigenomic differences.
Human DNA methylomes at base resolution show widespread epigenomic differences.
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DNA胞嘧啶甲基化是一种重要的表观遗传修饰，在基因组调控、发育和疾病等细胞过程中发挥重要作用。在这里，我们提出了第一个全基因组，单碱基分辨率地图的甲基化胞嘧啶在哺乳动物基因组中，从人类胚胎干细胞和胎儿成纤维细胞，沿着比较分析的mRNA和小RNA成分的转录组，几个组蛋白修饰，和几个关键的调控因子的DNA-蛋白质相互作用的网站。在两个基因组之间的胞嘧啶甲基化的组成和模式中确定了广泛的差异。在胚胎干细胞中发现的所有甲基化中，近四分之一是在非CG背景下，这表明它们可能利用不同的甲基化机制来影响基因调控。在非CG背景下的甲基化显示基因体的富集和蛋白结合位点和增强子的耗尽。非CG甲基化在胚胎干细胞诱导分化后消失，并在诱导多能干细胞中恢复。我们发现了数百个与多能性和分化相关的基因近端的差异甲基化区域，以及与较低转录活性相关的成纤维细胞中广泛降低的甲基化水平。这些参考表观基因组为未来研究探索人类疾病和发育中的这种关键表观遗传修饰提供了基础。
DNA cytosine methylation is a central epigenetic modification that plays essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of mRNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that they may utilize different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.
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影响因子：
46.9
作者：
Deng, Jie;Shoemaker, Robert;Xie, Bin;Gore, Athurva;LeProust, Emily M.;Antosiewicz-Bourget, Jessica;Egli, Dieter;Maherali, Nimet;Park, In-Hyun;Yu, Junying;Daley, George Q.;Eggan, Kevin;Hochedlinger, Konrad;Thomson, James;Wang, Wei;Gao, Yuan;Zhang, Kun
通讯作者：
Zhang, Kun
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
影响因子：
64.8
作者：
Hark, AT;Schoenherr, CJ;Tilghman, SM
通讯作者：
Tilghman, SM
影响因子：
56.9
作者：
Hellman, Asaf;Chess, Andrew
通讯作者：
Chess, Andrew