Genome-scale DNA methylation maps of pluripotent and differentiated cells.
Genome-scale DNA methylation maps of pluripotent and differentiated cells.
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DOI：
10.1038/nature07107
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发表时间：
2008-08-07
期刊：
影响因子：
64.8
通讯作者：
Lander, Eric S.
中科院分区：
文献类型：
--
作者：
Meissner, Alexander;Mikkelsen, Tarjei S.;Gu, Hongcang;Wernig, Marius;Hanna, Jacob;Sivachenko, Andrey;Zhang, Xiaolan;Bernstein, Bradley E.;Nusbaum, Chad;Jaffe, David B.;Gnirke, Andreas;Jaenisch, Rudolf;Lander, Eric S.
DNA甲基化对于正常发育至关重要，并且在包括癌症在内的许多病理中已经实施。在这里，我们报告了使用哺乳动物细胞中核动物分辨率的基因组尺度DNA甲基化的产生和分析高通量减少了代表性的Bisulphite测序和基于单分子的测序，我们生成了涵盖大多数CPG岛的DNA甲基化图，以及对保守的非编码元件，转座子和其他基因组特征的代表性采样，用于小鼠胚胎干细胞，胚胎 - 胚胎 - 胚胎 - 胚胎 - 胚胎 - 茎源性和原代神经细胞，其他八个主要组织。与基因组序列的背景相比，与基因组序列相比，CPG的甲基化是动态的表观遗传标记，在细胞分化过程中经历了广泛的变化，尤其是在核心启动子之外的调节区域。原代细胞表明，与特定受调节基因的特定基因相关的“弱” CpG岛发生异常在某些原发性肿瘤中报道的情况下，体外增生期间的高甲基化，结果是降低的代表性亚硫酸盐测序，作为与发育生物学，癌症和再生医学相关的细胞种群表观遗传分析的强大技术。
DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. Our knowledge about the genome-wide distribution of DNA methylation, how it changes during cellular differentiation and how it relates to histone methylation and other chromatin modifications in mammals remains limited. Here we report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput reduced representation bisulphite sequencing and single-molecule-based sequencing, we generated DNA methylation maps covering most CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for mouse embryonic stem cells, embryonic-stem-cell-derived and primary neural cells, and eight other primary tissues. Several key findings emerge from the data. First, DNA methylation patterns are better correlated with histone methylation patterns than with the underlying genome sequence context. Second, methylation of CpGs are dynamic epigenetic marks that undergo extensive changes during cellular differentiation, particularly in regulatory regions outside of core promoters. Third, analysis of embryonic-stem-cell-derived and primary cells reveals that ‘weak’ CpG islands associated with a specific set of developmentally regulated genes undergo aberrant hypermethylation during extended proliferation in vitro, in a pattern reminiscent of that reported in some primary tumours. More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine.
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DOI：
10.1073/pnas.1734197100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Aubert, J;Stavridis, MP;Smith, A
通讯作者：
Smith, A
影响因子：
10.5
作者：
Esteve, Pierre-Olivier;Chin, Hang Gyeong;Pradhan, Sriharsa
通讯作者：
Pradhan, Sriharsa
影响因子：
9.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Altshuler, D;Pollara, VJ;Lander, ES
通讯作者：
Lander, ES
影响因子：
7.5
作者：
Edwards, Carol A.;Ferguson-Smith, Anne C.
通讯作者：
Ferguson-Smith, Anne C.