Integrative analysis of 111 reference human epigenomes.

Nature

Authors	Roadmap Epigenomics Consortium Anshul Kundaje Wouter Meuleman Jason Ernst Misha Bilenky Angela Yen Alireza Heravi-Moussavi Pouya Kheradpour Zhizhuo Zhang Jianrong Wang Michael Ziller Viren Amin John Whitaker Matthew Schultz Lucas Ward Abhishek Sarkar Gerald Quon Richard Sandstrom Matthew Eaton Yi-Chieh Wu Andreas Pfenning Xinchen Wang Melina Claussnitzer Yaping Liu Cristian Coarfa R Alan Harris Noam Shoresh Charles Epstein Elizabeta Gjoneska Danny Leung Wei Xie R David Hawkins Ryan Lister Chibo Hong Philippe Gascard Andrew Mungall Richard Moore Eric Chuah Angela Tam Theresa Canfield R Scott Hansen Rajinder Kaul Peter Sabo Mukul Bansal Annaick Carles Jesse Dixon Kai-How Farh Soheil Feizi Rosa Karlić Ah-Ram Kim Ashwinikumar Kulkarni Daofeng Li Rebecca Lowdon GiNell Elliott Tim Mercer Shane Neph Vitor Onuchic Paz Polak Nisha Rajagopal Pradipta Ray Richard Sallari Kyle Siebenthall Nicholas Sinnott-Armstrong Michael Stevens Robert Thurman Jie Wu Bo Zhang Xin Zhou Arthur Beaudet Laurie Boyer Philip De Jager Peggy Farnham Susan Fisher David Haussler Steven Jones Wei Li Marco Marra Michael McManus Shamil Sunyaev James Thomson Thea Tlsty Li-Huei Tsai Wei Wang Robert Waterland Michael Zhang Lisa Chadwick Bradley Bernstein Joseph Costello Joseph Ecker Martin Hirst Alexander Meissner Aleksandar Milosavljevic Bing Ren John Stamatoyannopoulos Ting Wang Manolis Kellis
Keywords	Humans Base Sequence Cell Lineage DNA RNA Organ Specificity DNA Methylation Genome-Wide Association Study Genetic Variation Chromatin Enhancer Elements, Genetic Histones Cells, Cultured Epigenesis, Genetic Chromosomes, Human Genome, Human Datasets as Topic Epigenomics Reference Values
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.
Year of Publication	2015
Journal	Nature
Volume	518
Issue	7539
Pages	317-30
Date Published	2015 Feb 19
ISSN	1476-4687
URL
DOI	10.1038/nature14248
PubMed ID	25693563
PubMed Central ID	PMC4530010
Links
Grant list	U01 AG046152 / AG / NIA NIH HHS / United States U01ES017166 / ES / NIEHS NIH HHS / United States RF1 AG015819 / AG / NIA NIH HHS / United States F32 HL110473 / HL / NHLBI NIH HHS / United States R01 ES024984 / ES / NIEHS NIH HHS / United States U01 ES017154 / ES / NIEHS NIH HHS / United States R01 HG004037 / HG / NHGRI NIH HHS / United States R01 HG007175 / HG / NHGRI NIH HHS / United States U01ES017155 / ES / NIEHS NIH HHS / United States U01 DA025956 / DA / NIDA NIH HHS / United States F32HL110473 / HL / NHLBI NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R01HG004037 / HG / NHGRI NIH HHS / United States R01AG17917 / AG / NIA NIH HHS / United States U01ES017154 / ES / NIEHS NIH HHS / United States P01 DA008227 / DA / NIDA NIH HHS / United States T32 ES007032 / ES / NIEHS NIH HHS / United States ES017166 / ES / NIEHS NIH HHS / United States R01HG004037-S1 / HG / NHGRI NIH HHS / United States R01 NS078839 / NS / NINDS NIH HHS / United States U01AG46152 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States K99 HL119617 / HL / NHLBI NIH HHS / United States R01AG15819 / AG / NIA NIH HHS / United States Howard Hughes Medical Institute / United States R24 HD000836 / HD / NICHD NIH HHS / United States R01 ES024992 / ES / NIEHS NIH HHS / United States P50 MH096890 / MH / NIMH NIH HHS / United States R01NS078839 / NS / NINDS NIH HHS / United States RC1 HG005334 / HG / NHGRI NIH HHS / United States U01 ES017156 / ES / NIEHS NIH HHS / United States P30AG10161 / AG / NIA NIH HHS / United States U54 HG007990 / HG / NHGRI NIH HHS / United States T32 GM081739 / GM / NIGMS NIH HHS / United States T32 GM007266 / GM / NIGMS NIH HHS / United States 5R24HD000836 / HD / NICHD NIH HHS / United States U01 ES017166 / ES / NIEHS NIH HHS / United States R25 DA027995 / DA / NIDA NIH HHS / United States U01ES017156 / ES / NIEHS NIH HHS / United States U01 ES017155 / ES / NIEHS NIH HHS / United States U01DA025956 / DA / NIDA NIH HHS / United States R01 HG007354 / HG / NHGRI NIH HHS / United States U54 DK106829 / DK / NIDDK NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States T32 GM007198 / GM / NIGMS NIH HHS / United States K99HL119617 / HL / NHLBI NIH HHS / United States RC1HG005334 / HG / NHGRI NIH HHS / United States