Integrative analysis of 111 reference human epigenomes

作者：Anshul Kundaje, Wouter Meuleman, Jason Ernst, Misha Bilenky, Angela Yen, Alireza Heravi‐Moussavi, Pouya Kheradpour, Zhizhuo Zhang, Jianrong Wang, Michael J. Ziller, Viren R. Amin, John W. Whitaker, Matthew D. Schultz, Lucas D. Ward, Abhishek Sarkar, Gerald Quon, Richard S. Sandstrom, Matthew L. Eaton, Yi-Chieh Wu, Andreas R. Pfenning, Xinchen Wang, Melina Claussnitzer, Yaping Liu, Cristian Coarfa, Ronald Alan Harris, Noam Shoresh, Charles B. Epstein, Elizabeta Gjoneska, Danny Leung, Wei Xie, R. David Hawkins, Ryan Lister, Chibo Hong, Philippe D. Gascard, Andrew J. J. Mungall, Richard A. Moore, Eric Chuah, Angela Tam, Theresa K. Canfield, R. Scott Hansen, Rajinder Kaul, Peter J. Sabo, Mukul Subodh Bansal, Annaïck Carles, Jesse R. Dixon, Kai-How Farh, Soheil Feizi, Rosa Karlić, Ah-Ram Kim, Ashwinikumar Kulkarni, Daofeng Li, Rebecca F. Lowdon, GiNell Elliott, Tim R. Mercer, Shane J. Neph, Vitor Onuchic, Paz P Polak, Nisha Rajagopal, Pradipta R. Ray, Richard C. Sallari, Kyle T. Siebenthall, Nicholas A. Sinnott‐Armstrong, Michael W. Stevens, Robert E. Thurman, Jie Wu, Bo Zhang, Xin Zhou, Arthur E. Beaudet, Laurie A. Boyer, Philip L. De Jager, Peggy Farnham, Susan J. Fisher, David H. Haussler, Steven J.M. Jones, Wei Li, Marco A. Marra, Michael T. McManus, Shamil R. Sunyaev, James Alexander Thomson, Thea Dorothy Tlsty, Li-Huei Tsai, Wei Qiang Wang, Robert A. Waterland, Michael Q. Zhang, Lisa Helbling Chadwick, B Bernstein, J Costello, Joseph R. Ecker, Martin Hirst, Alexander Meissner, Aleksandar Milosavljević, Bing Ren, John A. Stamatoyannopoulos, Ting Wang, Manolis Kellis · 发表于：Nature · 年份：2015 · DOI：10.1038/nature14248 · 被引用次数：7250 · 研究领域：Epigenetics and DNA Methylation、Genomics and Chromatin Dynamics、RNA modifications and cancer

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, 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. This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the mole...