Integrative analysis of 111 reference human epigenomes

被引：4270

作者：

Kundaje, Anshul ^{[1
,2
,3
]}

Meuleman, Wouter ^{[1
,2
]}

Ernst, Jason ^{[1
,2
,4
]}

Bilenky, Misha ^{[5
]}

Yen, Angela ^{[1
,2
]}

Heravi-Moussavi, Alireza ^{[5
]}

Kheradpour, Pouya ^{[1
,2
]}

Zhang, Zhizhuo ^{[1
,2
]}

Wang, Jianrong ^{[1
,2
]}

Ziller, Michael J. ^{[2
,6
]}

Amin, Viren ^{[7
]}

Whitaker, John W. ^{[8
]}

Schultz, Matthew D. ^{[9
,10
]}

Ward, Lucas D. ^{[1
,2
]}

Sarkar, Abhishek ^{[1
,2
]}

Quon, Gerald ^{[1
,2
]}

Sandstrom, Richard S. ^{[11
]}

Eaton, Matthew L. ^{[1
,2
]}

Wu, Yi-Chieh ^{[1
,2
]}

Pfenning, Andreas R. ^{[1
,2
]}

Wang, Xinchen ^{[1
,2
,12
]}

Claussnitzer, Melina ^{[1
,2
]}

Liu, Yaping ^{[1
,2
]}

Coarfa, Cristian ^{[7
]}

Harris, R. Alan ^{[7
]}

Shoresh, Noam ^{[2
]}

Epstein, Charles B. ^{[2
]}

Gjoneska, Elizabeta ^{[2
,13
]}

Leung, Danny ^{[8
,14
]}

Xie, Wei ^{[8
,14
]}

Hawkins, R. David ^{[8
,14
]}

Lister, Ryan ^{[9
,10
]}

Hong, Chibo ^{[15
]}

Gascard, Philippe ^{[16
]}

Mungall, Andrew J. ^{[5
]}

Moore, Richard ^{[5
]}

Chuah, Eric ^{[5
]}

Tam, Angela ^{[5
]}

Canfield, Theresa K. ^{[11
]}

Hansen, R. Scott ^{[17
]}

Kaul, Rajinder ^{[17
]}

Sabo, Peter J. ^{[11
]}

Bansal, Mukul S. ^{[1
,2
,18
]}

Carles, Annaick ^{[19
,20
]}

Dixon, Jesse R. ^{[8
,14
]}

Farh, Kai-How ^{[2
]}

Feizi, Soheil ^{[1
,2
]}

Karlic, Rosa ^{[21
]}

Kim, Ah-Ram ^{[1
,2
]}

Kulkarni, Ashwinikumar ^{[22
]}

机构：

[1] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[2] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[3] Stanford Univ, Dept Genet, Dept Comp Sci, Stanford, CA 94305 USA

[4] Univ Calif Davis, Dept Biol Chem, Los Angeles, CA 90095 USA

[5] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada

[6] Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[7] Baylor Coll Med, Epigenome Ctr, Houston, TX 77030 USA

[8] Univ Calif San Diego, Inst Genom Med, Dept Cellular & Mol Med, Dept Chem & Biochem, La Jolla, CA 92093 USA

[9] Howard Hughes Med Inst, Genom Anal Lab, La Jolla, CA 92037 USA

[10] Salk Inst Biol Studies, La Jolla, CA 92037 USA

[11] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[12] MIT, Dept Biol, Cambridge, MA 02142 USA

[13] MIT, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA

[14] Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[15] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Neurosurg, San Francisco, CA 94158 USA

[16] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA

[17] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98121 USA

[18] Univ Connecticut, Dept Comp Sci & Engn, Storrs, CT 06269 USA

[19] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z4, Canada

[20] Univ British Columbia, Ctr High Throughput Biol, Vancouver, BC V6T 1Z4, Canada

[21] Univ Zagreb, Div Biol, Dept Mol Biol, Bioinformat Grp, Zagreb 10000, Croatia

[22] Univ Texas Dallas, Dept Mol & Cell Biol, Ctr Syst Biol, NSERL, Dallas, TX 75080 USA

[23] Washington Univ, Dept Genet, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA

[24] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia

[25] Brigham & Womens Hosp, Boston, MA 02115 USA

[26] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA

[27] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[28] Baylor Coll Med, Mol & Human Genet Dept, Houston, TX 77030 USA

[29] Harvard Univ, Sch Med, Boston, MA 02115 USA

[30] Univ So Calif, Keck Sch Med, Dept Biochem, Los Angeles, CA 90089 USA

[31] Univ Calif San Francisco, San Francisco, CA 94143 USA

[32] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA

[33] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada

[34] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z4, Canada

[35] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[36] Univ Calif San Francisco, Ctr Diabet, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[37] Univ Wisconsin, Madison, WI 53715 USA

[38] Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA

[39] Tsinghua Univ, Bioinformat Div, Ctr Synthet & Syst Biol, TNLIST, Beijing 100084, Peoples R China

[40] NIEHS, Res Triangle Pk, NC 27709 USA

[41] Massachusetts Gen Hosp, Boston, MA 02114 USA

[42] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[43] Morgridge Inst Res, Madison, WI 53707 USA

[44] Washington Univ, Dept Comp Sci & Engn, St Louis, MO 63130 USA

来源：

NATURE | 2015年 / 518卷 / 7539期

基金：

美国国家科学基金会;

关键词：

GENOME-WIDE ASSOCIATION; DYNAMIC DNA METHYLATION; CHROMATIN-STATE; HISTONE MODIFICATIONS; REGULATORY MOTIFS; BINDING; RISK; RESOLUTION; METAANALYSIS; ENHANCERS;

D O I：

10.1038/nature14248

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：317 / 330

页数：14

共 112 条

[1]

Amin V., 2011, NATURE COMM IN PRESS

[2] HIGH-LEVELS OF DENOVO METHYLATION AND ALTERED CHROMATIN STRUCTURE AT CPG ISLANDS IN CELL-LINES [J].

ANTEQUERA, F ;

BOYES, J ;

BIRD, A .

CELL, 1990, 62 (03) :503-514

[3] Gene Ontology: tool for the unification of biology [J].

Ashburner, M ;

Ball, CA ;

Blake, JA ;

Botstein, D ;

Butler, H ;

Cherry, JM ;

Davis, AP ;

Dolinski, K ;

Dwight, SS ;

Eppig, JT ;

Harris, MA ;

Hill, DP ;

Issel-Tarver, L ;

Kasarskis, A ;

Lewis, S ;

Matese, JC ;

Richardson, JE ;

Ringwald, M ;

Rubin, GM ;

Sherlock, G .

NATURE GENETICS, 2000, 25 (01) :25-29

[4] Diversity and Complexity in DNA Recognition by Transcription Factors [J].

Badis, Gwenael ;

Berger, Michael F. ;

Philippakis, Anthony A. ;

Talukder, Shaheynoor ;

Gehrke, Andrew R. ;

Jaeger, Savina A. ;

Chan, Esther T. ;

Metzler, Genita ;

Vedenko, Anastasia ;

Chen, Xiaoyu ;

Kuznetsov, Hanna ;

Wang, Chi-Fong ;

Coburn, David ;

Newburger, Daniel E. ;

Morris, Quaid ;

Hughes, Timothy R. ;

Bulyk, Martha L. .

SCIENCE, 2009, 324 (5935) :1720-1723

[5]

Bar-Joseph Z., 2001, BIOINFORMATICS S1, V17, pS22, DOI [DOI 10.1093/BIOINFORMATICS/17.SUPPL_1.S22, 10.1093/bioinformatics/17.suppl_1.S225]

[6] Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes [J].

Barrett, Jeffrey C. ;

Clayton, David G. ;

Concannon, Patrick ;

Akolkar, Beena ;

Cooper, Jason D. ;

Erlich, Henry A. ;

Julier, Cecile ;

Morahan, Grant ;

Nerup, Jorn ;

Nierras, Concepcion ;

Plagnol, Vincent ;

Pociot, Flemming ;

Schuilenburg, Helen ;

Smyth, Deborah J. ;

Stevens, Helen ;

Todd, John A. ;

Walker, Neil M. ;

Rich, Stephen S. .

NATURE GENETICS, 2009, 41 (06) :703-707

[7] High-resolution profiling of histone methylations in the human genome [J].

Barski, Artern ;

Cuddapah, Suresh ;

Cui, Kairong ;

Roh, Tae-Young ;

Schones, Dustin E. ;

Wang, Zhibin ;

Wei, Gang ;

Chepelev, Iouri ;

Zhao, Keji .

CELL, 2007, 129 (04) :823-837

[8] Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences [J].

Berger, Michael F. ;

Badis, Gwenael ;

Gehrke, Andrew R. ;

Talukder, Shaheynoor ;

Philippakis, Anthony A. ;

Pena-Castillo, Lourdes ;

Alleyne, Trevis M. ;

Mnaimneh, Sanie ;

Botvinnik, Olga B. ;

Chan, Esther T. ;

Khalid, Faiqua ;

Zhang, Wen ;

Newburger, Daniel ;

Jaeger, Savina A. ;

Morris, Quaid D. ;

Bulyk, Martha L. ;

Hughes, Timothy R. .

CELL, 2008, 133 (07) :1266-1276

[9] Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities [J].

Berger, Michael F. ;

Philippakis, Anthony A. ;

Qureshi, Aaron M. ;

He, Fangxue S. ;

Estep, Preston W., III ;

Bulyk, Martha L. .

NATURE BIOTECHNOLOGY, 2006, 24 (11) :1429-1435

[10] Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia [J].

Berndt, Sonja I. ;

Skibola, Christine F. ;

Joseph, Vijai ;

Camp, Nicola J. ;

Nieters, Alexandra ;

Wang, Zhaoming ;

Cozen, Wendy ;

Monnereau, Alain ;

Wang, Sophia S. ;

Kelly, Rachel S. ;

Lan, Qing ;

Teras, Lauren R. ;

Chatterjee, Nilanjan ;

Chung, Charles C. ;

Yeager, Meredith ;

Brooks-Wilson, Angela R. ;

Hartge, Patricia ;

Purdue, Mark P. ;

Birmann, Brenda M. ;

Armstrong, Bruce K. ;

Cocco, Pierluigi ;

Zhang, Yawei ;

Severi, Gianluca ;

Zeleniuch-Jacquotte, Anne ;

Lawrence, Charles ;

Burdette, Laurie ;

Yuenger, Jeffrey ;

Hutchinson, Amy ;

Jacobs, Kevin B. ;

Call, Timothy G. ;

Shanafelt, Tait D. ;

Novak, Anne J. ;

Kay, Neil E. ;

Liebow, Mark ;

Wang, Alice H. ;

Smedby, Karin E. ;

Adami, Hans-Olov ;

Melbye, Mads ;

Glimelius, Bengt ;

Chang, Ellen T. ;

Glenn, Martha ;

Curtin, Karen ;

Cannon-Albright, Lisa A. ;

Jones, Brandt ;

Diver, W. Ryan ;

Link, Brian K. ;

Weiner, George J. ;

Conde, Lucia ;

Bracci, Paige M. ;

Riby, Jacques .

NATURE GENETICS, 2013, 45 (08) :868-876

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