Integrative analysis of 111 reference human epigenomes.
Integrative analysis of 111 reference human epigenomes.
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DOI：
10.1038/nature14248
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发表时间：
2015-02-19
期刊：
影响因子：
64.8
通讯作者：
Kellis M
中科院分区：
文献类型：
--
作者：
Roadmap Epigenomics Consortium;Kundaje A;Meuleman W;Ernst J;Bilenky M;Yen A;Heravi-Moussavi A;Kheradpour P;Zhang Z;Wang J;Ziller MJ;Amin V;Whitaker JW;Schultz MD;Ward LD;Sarkar A;Quon G;Sandstrom RS;Eaton ML;Wu YC;Pfenning AR;Wang X;Claussnitzer M;Liu Y;Coarfa C;Harris RA;Shoresh N;Epstein CB;Gjoneska E;Leung D;Xie W;Hawkins RD;Lister R;Hong C;Gascard P;Mungall AJ;Moore R;Chuah E;Tam A;Canfield TK;Hansen RS;Kaul R;Sabo PJ;Bansal MS;Carles A;Dixon JR;Farh KH;Feizi S;Karlic R;Kim AR;Kulkarni A;Li D;Lowdon R;Elliott G;Mercer TR;Neph SJ;Onuchic V;Polak P;Rajagopal N;Ray P;Sallari RC;Siebenthall KT;Sinnott-Armstrong NA;Stevens M;Thurman RE;Wu J;Zhang B;Zhou X;Beaudet AE;Boyer LA;De Jager PL;Farnham PJ;Fisher SJ;Haussler D;Jones SJ;Li W;Marra MA;McManus MT;Sunyaev S;Thomson JA;Tlsty TD;Tsai LH;Wang W;Waterland RA;Zhang MQ;Chadwick LH;Bernstein BE;Costello JF;Ecker JR;Hirst M;Meissner A;Milosavljevic A;Ren B;Stamatoyannopoulos JA;Wang T;Kellis M
参考人类基因组序列为研究遗传变异及其与人类疾病的关联的研究奠定了基础，但是缺乏类似的参考。为了满足这一需求，NIH路线图表观基因组学财团产生了针对原代细胞和组织的人类表观基因组最大的收集。在这里，我们描述了作为该程序的一部分产生的111个参考人类表观基因瘤的综合分析，介绍了组蛋白修饰模式，DNA可及性，DNA甲基化和RNA表达。我们建立了监管要素的全球图，定义了协调活动的监管模块及其可能的激活因素和阻遏物。我们表明，疾病和与性状相关的遗传变异富含组织特异性表观基因组学标记，揭示了与生物学上的细胞类型有关多种人类性状的细胞类型，并提供了解释人类疾病分子基础的资源。我们的结果表明，表观基因组信息在理解基因调节，细胞分化和人类疾病方面的核心作用。
The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but a similar reference has lacked for epigenomic studies. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection to-date of human epigenomes for primary cells and tissues. Here, we describe the integrative analysis of 111 reference human epigenomes generated as part of the program, profiled for histone modification patterns, DNA accessibility, DNA methylation, and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically-relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation, and human disease.