Dynamic DNA methylation across diverse human cell lines and tissues.
Dynamic DNA methylation across diverse human cell lines and tissues.
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DOI：
10.1101/gr.147942.112
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发表时间：
2013-03
期刊：
影响因子：
7
通讯作者：
Myers RM
中科院分区：
文献类型：
--
作者：
Varley KE;Gertz J;Bowling KM;Parker SL;Reddy TE;Pauli-Behn F;Cross MK;Williams BA;Stamatoyannopoulos JA;Crawford GE;Absher DM;Wold BJ;Myers RM
随着 DNA 甲基化研究范围的扩大，人们发现甲基化与基因表达有着复杂的关系，在定义细胞类型中发挥着重要作用，并且在许多疾病中受到破坏。我们使用简化代表性亚硫酸氢盐测序 (RRBS) 对 82 种不同的人类细胞系和组织进行大规模单碱基分辨率 DNA 甲基化分析。整合 RNA-seq 和 ChIP-seq 数据的分析阐明了该动态标记的功能作用。跨癌症类型的高甲基化基因座在胚胎干细胞中富含 NANOG 结合位点，这支持并扩展了癌症中干细胞/祖细胞特征的模型。跨癌症类型低甲基化的 CpG 集中在染色体端粒和着丝粒附近的兆碱基级结构域中，基因被耗尽，并且富含癌症特异性 EZH2 结合和 H3K27me3（抑制性染色质）。在非癌症样本中，原代细胞系和组织中保留了细胞类型特异性甲基化特征，以及细胞培养诱导的甲基化差异。甲基化和表达之间的关系是上下文相关的，我们发现表达基因体内与 EP300 结合的富含 CpG 的增强子并未甲基化，尽管它们周围有密集的基因体甲基化。非 CpG 胞嘧啶甲基化发生在人体组织中，在脑组织中尤其普遍，并且在许多个体中可重复。这项研究提供了跨不同且特征明确的样本的 DNA 甲基化图谱，并使得有关 DNA 甲基化及其在基因调控和疾病中的作用的新发现成为可能。
As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is disrupted in many diseases. We describe large-scale single-base resolution DNA methylation profiling on a diverse collection of 82 human cell lines and tissues using reduced representation bisulfite sequencing (RRBS). Analysis integrating RNA-seq and ChIP-seq data illuminates the functional role of this dynamic mark. Loci that are hypermethylated across cancer types are enriched for sites bound by NANOG in embryonic stem cells, which supports and expands the model of a stem/progenitor cell signature in cancer. CpGs that are hypomethylated across cancer types are concentrated in megabase-scale domains that occur near the telomeres and centromeres of chromosomes, are depleted of genes, and are enriched for cancer-specific EZH2 binding and H3K27me3 (repressive chromatin). In noncancer samples, there are cell-type specific methylation signatures preserved in primary cell lines and tissues as well as methylation differences induced by cell culture. The relationship between methylation and expression is context-dependent, and we find that CpG-rich enhancers bound by EP300 in the bodies of expressed genes are unmethylated despite the dense gene-body methylation surrounding them. Non-CpG cytosine methylation occurs in human somatic tissue, is particularly prevalent in brain tissue, and is reproducible across many individuals. This study provides an atlas of DNA methylation across diverse and well-characterized samples and enables new discoveries about DNA methylation and its role in gene regulation and disease.
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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：
7
作者：
Hon, Gary C.;Hawkins, R. David;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
7
作者：
Easwaran, Hariharan;Johnstone, Sarah E.;Baylin, Stephen B.
通讯作者：
Baylin, Stephen B.
影响因子：
4.5
作者：
Gertz J;Varley KE;Reddy TE;Bowling KM;Pauli F;Parker SL;Kucera KS;Willard HF;Myers RM
通讯作者：
Myers RM
高CpG岛甲基化表型与胃癌淋巴结转移和预后相关
影响因子：
5.7
作者：
Chen, Hua-Yun;Zhu, Bao-He;He, Yu-Long
通讯作者：
He, Yu-Long