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Nature DOI:10.1038/nature14248

Integrative analysis of 111 reference human epigenomes.

Publication TypeJournal Article
Year of Publication2015
AuthorsKundaje, 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, Y-C, Pfenning, AR, Wang, X, Claussnitzer, M, Liu, Y, Coarfa, C, R Harris, A, Shoresh, N, Epstein, CB, Gjoneska, E, Leung, D, Xie, W, R Hawkins, D, Lister, R, Hong, C, Gascard, P, Mungall, AJ, Moore, R, Chuah, E, Tam, A, Canfield, TK, R Hansen, S, Kaul, R, Sabo, PJ, Bansal, MS, Carles, A, Dixon, JR, Farh, K-H, Feizi, S, Karlić, R, Kim, A-R, Kulkarni, A, Li, D, Lowdon, R, Elliott, GN, 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, SJM, Li, W, Marra, MA, McManus, MT, Sunyaev, S, Thomson, JA, Tlsty, TD, Tsai, L-H, 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
Corporate AuthorsRoadmap Epigenomics Consortium
JournalNature
Volume518
Issue7539
Pages317-30
Date Published2015 Feb 19
ISSN1476-4687
KeywordsBase Sequence, Cell Lineage, Cells, Cultured, Chromatin, Chromosomes, Human, Datasets as Topic, DNA, DNA Methylation, Enhancer Elements, Genetic, Epigenesis, Genetic, Epigenomics, Genetic Variation, Genome, Human, Genome-Wide Association Study, Histones, Humans, Organ Specificity, Reference Values, RNA
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.

URLhttp://dx.doi.org/10.1038/nature14248
DOI10.1038/nature14248
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25693563?dopt=Abstract

Alternate JournalNature
PubMed ID25693563
PubMed Central IDPMC4530010
Grant ListU01 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