Integrative analysis of 111 reference human epigenomes
Anshul Kundaje(Vassar College), Wouter Meuleman(Broad Institute), Jason Ernst(Vassar College), Misha Bilenky(BC Cancer Agency), Angela Yen(Broad Institute), Alireza Heravi‐Moussavi(BC Cancer Agency), Pouya Kheradpour(Broad Institute), Zhizhuo Zhang(Broad Institute), Jianrong Wang(Broad Institute), Michael J. Ziller(Broad Institute), Viren Amin(Baylor College of Medicine), John W. Whitaker(University of California San Diego), Matthew D. Schultz(Salk Institute for Biological Studies), Lucas D. Ward(Broad Institute), Abhishek Sarkar(Broad Institute), Gerald Quon(Broad Institute), Richard Sandstrom(University of Washington), Matthew L. Eaton(Broad Institute), Yi-Chieh Wu(Broad Institute), Andreas R. Pfenning(Broad Institute), Xinchen Wang(Vassar College), Melina Claussnitzer(Broad Institute), Yaping Liu(Broad Institute), Cristian Coarfa(Baylor College of Medicine), R. Alan Harris(Baylor College of Medicine), Noam Shoresh(Broad Institute), Charles B. Epstein(Broad Institute), Elizabeta Gjoneska(Broad Institute), Danny Leung(University of California San Diego), Wei Xie(University of California San Diego), R. David Hawkins(University of California San Diego), Ryan Lister(Salk Institute for Biological Studies), Chibo Hong(University of California, San Francisco), Philippe Gascard(University of California, San Francisco), Andrew J. Mungall(BC Cancer Agency), Richard A. Moore(BC Cancer Agency), Eric Chuah(BC Cancer Agency), Angela Tam(BC Cancer Agency), Theresa K. Canfield(University of Washington), R. Scott Hansen(University of Washington Medical Center), Rajinder Kaul(University of Washington Medical Center), Peter J. Sabo(University of Washington), Mukul S. Bansal(Broad Institute), Annaïck Carles(University of British Columbia), Jesse R. Dixon(University of California San Diego), Kai-How Farh(Broad Institute), Soheil Feizi(Broad Institute), Rosa Karlić(University of Zagreb), Ah-Ram Kim(Broad Institute), Ashwinikumar Kulkarni(The University of Texas at Dallas), Daofeng Li(Washington University in St. Louis), Rebecca F. Lowdon(Washington University in St. Louis), GiNell Elliott(Washington University in St. Louis), Tim R. Mercer(The University of Queensland), Shane Neph(University of Washington), Vitor Onuchic(Baylor College of Medicine), Paz Polak(Broad Institute), Nisha Rajagopal(University of California San Diego), Pradipta Ray(The University of Texas at Dallas), Richard Sallari(Broad Institute), Kyle Siebenthall(University of Washington), Nicholas A. Sinnott‐Armstrong(Broad Institute), Michael Stevens(Washington University in St. Louis), Robert E. Thurman(University of Washington), Jie Wu(Stony Brook University), Bo Zhang(Washington University in St. Louis), Xin Zhou(Washington University in St. Louis), Arthur E. Beaudet(Baylor College of Medicine), Laurie A. Boyer(Massachusetts Institute of Technology), Philip L. De Jager(Broad Institute), Peggy Farnham(University of Southern California), Susan J. Fisher(University of California, San Francisco), David Haussler(University of California, Santa Cruz), Steven J.M. Jones(BC Cancer Agency), Wei Li(Baylor College of Medicine), Marco A. Marra(BC Cancer Agency), Michael T. McManus(University of California, San Francisco), Shamil Sunyaev(Broad Institute), James A. Thomson(University of Wisconsin–Madison), Thea D. Tlsty(University of California, San Francisco), Li-Huei Tsai(Broad Institute), Wei Wang(University of California San Diego), Robert A. Waterland(Children's Nutrition Research Center at Baylor College of Medicine), Michael Q. Zhang(The University of Texas at Dallas), Lisa H. Chadwick(National Institute of Environmental Health Sciences), B Bernstein(Broad Institute), J Costello(University of California, San Francisco), Joseph R. Ecker(Salk Institute for Biological Studies), Martin Hirst(University of British Columbia), Alexander Meissner, Aleksandar Milosavljević(Baylor College of Medicine), Bing Ren(Ludwig Cancer Research), J Stamatoyannopoulos(University of Washington), Ting Wang(Washington University in St. Louis), Manolis Kellis(Broad Institute)
Cited by 7,082Open Access
Abstract
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.
Related Papers
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Menno P. Creyghton, Albert W. Cheng, G. Grant Welstead et al.|Proceedings of the National Academy of Sciences|2010|4.5k