An integrated encyclopedia of DNA elements in the human genome

被引:12241
作者
Dunham, Ian [1 ]
Kundaje, Anshul [2 ]
Aldred, Shelley F. [3 ]
Collins, Patrick J. [3 ]
Davis, CarrieA. [4 ]
Doyle, Francis [5 ]
Epstein, Charles B. [6 ]
Frietze, Seth [7 ]
Harrow, Jennifer [8 ]
Kaul, Rajinder [9 ]
Khatun, Jainab [10 ]
Lajoie, Bryan R. [11 ]
Landt, Stephen G. [12 ]
Lee, Bum-Kyu [13 ]
Pauli, Florencia [14 ]
Rosenbloom, Kate R. [15 ]
Sabo, Peter [16 ]
Safi, Alexias [17 ]
Sanyal, Amartya [11 ]
Shoresh, Noam [6 ]
Simon, Jeremy M. [18 ]
Song, Lingyun [17 ]
Trinklein, Nathan D. [3 ]
Altshuler, Robert C. [19 ]
Birney, Ewan [1 ]
Brown, James B. [20 ]
Cheng, Chao [21 ]
Djebali, Sarah [22 ]
Dong, Xianjun [23 ]
Dunham, Ian [1 ]
Ernst, Jason [19 ]
Furey, Terrence S. [24 ]
Gerstein, Mark [21 ]
Giardine, Belinda [25 ]
Greven, Melissa [23 ]
Hardison, Ross C. [25 ,26 ]
Harris, Robert S. [25 ]
Herrero, Javier [1 ]
Hoffman, Michael M. [16 ]
Iyer, Sowmya [27 ]
Kellis, Manolis [19 ]
Khatun, Jainab [10 ]
Kheradpour, Pouya [19 ]
Kundaje, Anshul [2 ]
Lassmann, Timo [28 ]
Li, Qunhua [20 ]
Lin, Xinying [23 ]
Marinov, Georgi K. [29 ]
Merkel, Angelika [22 ]
Mortazavi, Ali [30 ]
机构
[1] European Bioinformat Inst EMBL EBI, Vertebrate Genom Grp, Hinxton CB10 1SD, Cambs, England
[2] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
[3] SwitchGear Genom, Menlo Pk, CA 94025 USA
[4] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[5] SUNY Albany, Albany, NY 12203 USA
[6] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
[7] USC Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA
[8] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England
[9] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA
[10] Boise State Univ, Coll Arts & Sci, Boise, ID 83725 USA
[11] Univ Massachusetts, Sch Med, Program Syst Biol, Program Gene Funct & Express,Dept Biochem & Mol P, Worcester, MA 01605 USA
[12] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[13] Univ Texas Austin, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, Sect Mol Genet & Microbiol, Austin, TX 78712 USA
[14] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA
[15] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA
[16] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[17] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA
[18] Univ N Carolina, Dept Biol, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA
[19] MIT, Comp Sci & Artificial Intelligence Lab, Broad Inst MIT & Harvard, Cambridge, MA 02139 USA
[20] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA
[21] Yale Univ, Computat Biol & Bioinformat Program, New Haven, CT 06520 USA
[22] Ctr Genom Regulat, Barcelona 08003, Catalonia, Spain
[23] Univ Massachusetts, Program Bioinformat & Integrat Biol, Sch Med, Worcester, MA 01605 USA
[24] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
[25] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA
[26] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA
[27] Boston Univ, Program Bioinformat, Boston, MA 02215 USA
[28] RIKEN Yokohama Inst, RIKEN Omics Sci Ctr, Tsurumi ku, Yokohama, Kanagawa 2300045, Japan
[29] CALTECH, Div Biol, Pasadena, CA 91125 USA
[30] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA 92697 USA
[31] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA
[32] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
[33] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA
[34] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
[35] Harvard Univ, Sch Med, Boston, MA 02114 USA
[36] NHGRI, NIH, Bethesda, MD 20892 USA
[37] NHGRI, NIH, Bethesda, MD 20892 USA
[38] NHGRI, NIH, Rockville, MD 20892 USA
[39] Affymetrix Inc, Santa Clara, CA 95051 USA
[40] Univ Pompeu Fabra, Dept Ciencies Expt Salut, Barcelona 08002, Catalonia, Spain
[41] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[42] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA
[43] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA
[44] CALTECH, Beckman Inst, Pasadena, CA 91125 USA
[45] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
[46] CNAG, Barcelona 08028, Catalonia, Spain
[47] Affymetrix Inc, Genom, Santa Clara, CA 95051 USA
[48] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland
[49] Genome Inst Singapore, Singapore 138672, Singapore
[50] Genome Inst Singapore, Singapore 138672, Singapore
基金
美国能源部;
关键词
TRANSCRIPTION FACTOR-BINDING; CHROMOSOME CONFORMATION CAPTURE; HUMAN-CELLS; IN-VIVO; CHROMATIN; REGIONS; MOUSE; MAPS; WIDE; DETERMINANTS;
D O I
10.1038/nature11247
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 human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.
引用
收藏
页码:57 / 74
页数:18
相关论文
共 75 条
[1]   A map of human genome variation from population-scale sequencing [J].
Altshuler, David ;
Durbin, Richard M. ;
Abecasis, Goncalo R. ;
Bentley, David R. ;
Chakravarti, Aravinda ;
Clark, Andrew G. ;
Collins, Francis S. ;
De la Vega, Francisco M. ;
Donnelly, Peter ;
Egholm, Michael ;
Flicek, Paul ;
Gabriel, Stacey B. ;
Gibbs, Richard A. ;
Knoppers, Bartha M. ;
Lander, Eric S. ;
Lehrach, Hans ;
Mardis, Elaine R. ;
McVean, Gil A. ;
Nickerson, DebbieA. ;
Peltonen, Leena ;
Schafer, Alan J. ;
Sherry, Stephen T. ;
Wang, Jun ;
Wilson, Richard K. ;
Gibbs, Richard A. ;
Deiros, David ;
Metzker, Mike ;
Muzny, Donna ;
Reid, Jeff ;
Wheeler, David ;
Wang, Jun ;
Li, Jingxiang ;
Jian, Min ;
Li, Guoqing ;
Li, Ruiqiang ;
Liang, Huiqing ;
Tian, Geng ;
Wang, Bo ;
Wang, Jian ;
Wang, Wei ;
Yang, Huanming ;
Zhang, Xiuqing ;
Zheng, Huisong ;
Lander, Eric S. ;
Altshuler, David L. ;
Ambrogio, Lauren ;
Bloom, Toby ;
Cibulskis, Kristian ;
Fennell, Tim J. ;
Gabriel, Stacey B. .
NATURE, 2010, 467 (7319) :1061-1073
[2]   Widely distributed noncoding purifying selection in the human genome [J].
Asthana, Saurabh ;
Noble, William S. ;
Kryukov, Gregory ;
Grantt, Charles E. ;
Sunyaev, Shamil ;
Stamatoyannopoulos, John A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (30) :12410-12415
[3]   Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells [J].
Ball, Madeleine P. ;
Li, Jin Billy ;
Gao, Yuan ;
Lee, Je-Hyuk ;
LeProust, Emily M. ;
Park, In-Hyun ;
Xie, Bin ;
Daley, George Q. ;
Church, George M. .
NATURE BIOTECHNOLOGY, 2009, 27 (04) :361-368
[4]   SUBSAMPLING METHODS FOR GENOMIC INFERENCE [J].
Bickel, Peter J. ;
Boley, Nathan ;
Brown, James B. ;
Huang, Haiyan ;
Zhang, Nancy R. .
ANNALS OF APPLIED STATISTICS, 2010, 4 (04) :1660-1697
[5]   Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].
Birney, Ewan ;
Stamatoyannopoulos, John A. ;
Dutta, Anindya ;
Guigo, Roderic ;
Gingeras, Thomas R. ;
Margulies, Elliott H. ;
Weng, Zhiping ;
Snyder, Michael ;
Dermitzakis, Emmanouil T. ;
Stamatoyannopoulos, John A. ;
Thurman, Robert E. ;
Kuehn, Michael S. ;
Taylor, Christopher M. ;
Neph, Shane ;
Koch, Christoph M. ;
Asthana, Saurabh ;
Malhotra, Ankit ;
Adzhubei, Ivan ;
Greenbaum, Jason A. ;
Andrews, Robert M. ;
Flicek, Paul ;
Boyle, Patrick J. ;
Cao, Hua ;
Carter, Nigel P. ;
Clelland, Gayle K. ;
Davis, Sean ;
Day, Nathan ;
Dhami, Pawandeep ;
Dillon, Shane C. ;
Dorschner, Michael O. ;
Fiegler, Heike ;
Giresi, Paul G. ;
Goldy, Jeff ;
Hawrylycz, Michael ;
Haydock, Andrew ;
Humbert, Richard ;
James, Keith D. ;
Johnson, Brett E. ;
Johnson, Ericka M. ;
Frum, Tristan T. ;
Rosenzweig, Elizabeth R. ;
Karnani, Neerja ;
Lee, Kirsten ;
Lefebvre, Gregory C. ;
Navas, Patrick A. ;
Neri, Fidencio ;
Parker, Stephen C. J. ;
Sabo, Peter J. ;
Sandstrom, Richard ;
Shafer, Anthony .
NATURE, 2007, 447 (7146) :799-816
[6]   Divergence of transcription factor binding sites across related yeast species [J].
Borneman, Anthony R. ;
Gianoulis, Tara A. ;
Zhang, Zhengdong D. ;
Yu, Haiyuan ;
Rozowsky, Joel ;
Seringhaus, Michael R. ;
Wang, Lu Yong ;
Gerstein, Mark ;
Snyder, Michael .
SCIENCE, 2007, 317 (5839) :815-819
[7]   High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells [J].
Boyle, Alan P. ;
Song, Lingyun ;
Lee, Bum-Kyu ;
London, Darin ;
Keefe, Damian ;
Birney, Ewan ;
Iyer, Vishwanath R. ;
Crawford, Gregory E. ;
Furey, Terrence S. .
GENOME RESEARCH, 2011, 21 (03) :456-464
[8]  
Boyle AP., 2012, GENOME RES
[9]  
Cheng C., 2012, GENOME RES
[10]   The share of human genomic DNA under selection estimated from human-mouse genomic alignments [J].
Chiaromonte, F ;
Weber, RJ ;
Roskin, KM ;
Diekhans, M ;
Kent, WJ ;
Haussler, D .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 2003, 68 :245-254