Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #319452
Title: Integrative analysis of 111 reference human epigenomes

Author
item KUNDAJE, ANSHUL - Massachusetts Institute Of Technology
item MEULEMAN, WOUTER - Massachusetts Institute Of Technology
item ERNST, JASON - Massachusetts Institute Of Technology
item YEN, ANGELA - Massachusetts Institute Of Technology
item KHERADPOUR, POUYA - Massachusetts Institute Of Technology
item ZHANGZHI, ZHUO - Massachusetts Institute Of Technology
item WANG, JIANRONG - Massachusetts Institute Of Technology
item ZILLER, MICHAEL - Massachusetts Institute Of Technology
item AMIN, VIREN - Baylor College Of Medicine
item WHITAKER, JOHN - University Of California
item SCHULTZ, MATTHEW - Howard Hughes Medical Institute
item WARD, LUCAS - Massachusetts Institute Of Technology
item SARKER, ABHISHEK - Massachusetts Institute Of Technology
item QUON, GERALD - Massachusetts Institute Of Technology
item SANDSTROM, RICHARD - University Of Washington
item EATON, MATTHEW - Massachusetts Institute Of Technology
item WU, YI-CHIEH - Massachusetts Institute Of Technology
item PFENNING, ANDREAS - Massachusetts Institute Of Technology
item WANG, XINCHEN - Massachusetts Institute Of Technology
item CLAUSSNITZER, MELINA - Massachusetts Institute Of Technology
item LIU, YAPING - Massachusetts Institute Of Technology
item COARFA, CHRISTIAN - Baylor College Of Medicine
item HARRIS, R. ALLAN - Baylor College Of Medicine
item SHORESH, NOAM - Massachusetts Institute Of Technology
item EPSTEIN, CHARLES - Broad Institute Of Mit/harvard
item GJONESKA, ELIZABETH - Broad Institute Of Mit/harvard
item LEUNG, DANNY - Ludwig Institute For Cancer Research
item XIE, WEI - Ludwig Institute For Cancer Research
item HAWKINS, R. DAVID - Ludwig Institute For Cancer Research
item LISTER, RYAN - Howard Hughes Medical Institute
item HONG, CHIBO - University Of California
item GASCARD, PHILIPPE - University Of California
item CANFIELD, THRESA - University Of Washington
item HANSEN, R. SCOTT - University Of Washington
item KAUL, RAJINDER - University Of Washington
item SABO, PETER - University Of Washington
item BANSAL, MUKUL - Massachusetts Institute Of Technology
item CARLES, ANNAICK - University Of British Columbia
item DIXON, JESSE - Ludwig Institute For Cancer Research
item FARTH, KAI-HOW - Broad Institute Of Mit/harvard
item FEIZI, SOHEIL - Massachusetts Institute Of Technology
item KARLIC, ROSA - University Of Zagreb
item KIM, AH-RAM - Massachusetts Institute Of Technology
item LI, DAOFENG - Washington University
item LOWDON, REBECCA - Washington University
item ELLIOTT, GINELL - Washington University
item MERCER, TIM - University Of Queensland
item NEPH, SHANE - University Of Washington
item ONUCHIC, VITOR - Baylor College Of Medicine
item POLAK, PAZ - Broad Institute Of Mit/harvard
item RAJAGOPAL, NISHA - University Of California
item RAY, PRADIPTA - University Of Texas Southwestern Medical Center
item SALLARI, RICHARD - Broad Institute Of Mit/harvard
item SIEBENTHALL, KYLE - University Of Washington
item SINNOTT-ARMSTRONG, NICHOLAS - Broad Institute Of Mit/harvard
item STEVENS, MICHAEL - University Of Washington
item THURMAN, ROBERT - University Of Washington
item WU, JIE - Cold Spring Harbor Laboratory
item ZHANG, BO - Washington University
item ZHOU, XIN - Washington University
item BEAUDET, ARTHUR - Baylor College Of Medicine
item BOYER, LAURIE - Massachusetts Institute Of Technology
item DE JAGER, PHILIP - Broad Institute Of Mit/harvard
item FARNHAM, PEGGY - University Of Southern California
item FISHER, SUSAN - University Of California
item HAUSSLER, DAVID - University Of Santa Cruz - Brazil
item JONES, STEVEN J. - University Of British Columbia
item LI, WEI - Baylor College Of Medicine
item MARRA, MARCO - University Of British Columbia
item MCMANUS, MICHAEL - University Of California
item SUNYAEV, SHAMIL - Broad Institute Of Mit/harvard
item THOMSON, JAMES - University Of Wisconsin
item TISTY, THEA - University Of California
item TSAI, LI-HUEI - Broad Institute Of Mit/harvard
item WANG, WEI - University Of California
item WATERLAND, ROBERT - Children'S Nutrition Research Center (CNRC)
item ZHANG, MICHAEL - Tsinghua University
item CHADWICK, LISA - National Institute Of Environmental Health Sciences (NIEHS, NIH)
item BERNSTEIN, BRADLEY - Broad Institute Of Mit/harvard
item COSTELLO, JOSEPH - University Of California
item ECKER, JOSEPH - Salk Institute Of Biological Studies
item HIRST, MARTIN - University Of British Columbia
item MEISSNER, ALEXANDER - Broad Institute Of Mit/harvard
item MILOSAVLJEVIC, ALEKSANDAR - Baylor College Of Medicine
item REN, BING - University Of California
item STAMATOYANNOPOULOS, JOHN - University Of Washington
item WANG, TING - Washington University
item KELLIS, MANOLIS - Massachusetts Institute Of Technology

Submitted to: Nature
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/21/2015
Publication Date: 2/19/2015
Citation: Kundaje, A., Meuleman, W., Ernst, J., Yen, A., Kheradpour, P., Zhangzhi, Z., Wang, J., Ziller, M.J., Amin, V., Whitaker, J.W., Schultz, M.D., Ward, L.D., Sarker, A., Quon, G., Sandstrom, R.S., Eaton, M.L., Wu, Y., Pfenning, A.R., Wang, X., Claussnitzer, M., Liu, Y., Coarfa, C., Harris, R., Shoresh, N., Epstein, C.B., Gjoneska, E., Leung, D., Xie, W., Hawkins, R., Lister, R., Hong, C., Gascard, P., Canfield, T.K., Hansen, R., Kaul, R., Sabo, P.J., Bansal, M.S., Carles, A., Dixon, J.R., Farth, K., Feizi, S., Karlic, R., Kim, A., Li, D., Lowdon, R., Elliott, G., Mercer, T.R., Neph, S.J., Onuchic, V., Polak, P., Rajagopal, N., Ray, P., Sallari, R.C., Siebenthall, K.T., Sinnott-Armstrong, N.A., Stevens, M., Thurman, R.E., Wu, J., Zhang, B., Zhou, X., Beaudet, A.E., Boyer, L.A., De Jager, P.L., Farnham, P.J., Fisher, S.J., Haussler, D., Jones, S.M., Li, W., Marra, M.A., Mcmanus, M.T., Sunyaev, S., Thomson, J.A., Tisty, T.D., Tsai, L., Wang, W., Waterland, R.A., Zhang, M.Q., Chadwick, L.H., Bernstein, B.E., Costello, J.F., Ecker, J.R., Hirst, M., Meissner, A., Milosavljevic, A., Ren, B., Stamatoyannopoulos, J.A., Wang, T., Kellis, M. 2015. Integrative analysis of 111 reference human epigenomes. Nature. 518(7539):317-330.

Interpretive Summary: At one time many hoped that the completion of the human genome project, which mapped out the genetic sequence of humans, would provide the keys to understand all of human disease. Now, we know that it is much more complicated. A major reason is that in addition to one's DNA sequence, stable differences in the way genes are used – so called 'epigenetic' differences – affect one's risk of disease. Unlike the DNA sequence, however, which is the same in every cell of the body, epigenetic mechanisms are specialized in different cell types. Moreover, epigenetic marks come in many 'flavors', including molecular mechanisms such as methylation (addition of a CH3 group) to DNA, and various modifications of the proteins that package DNA in each cell. To begin to illuminate all this complexity, the Roadmap Epigenomics Consortium mapped out several levels of epigenetic modifications across the genome in 111 different human tissues and cell types. This reference data set is presented and analyzed in this paper.

Technical 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.