Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-06

AUTHORS

Ewan Birney, John A. Stamatoyannopoulos, Anindya Dutta, Roderic Guigó, Thomas R. Gingeras, Elliott H. Margulies, Zhiping Weng, Michael Snyder, Emmanouil T. Dermitzakis, John A. Stamatoyannopoulos, Robert E. Thurman, Michael S. Kuehn, Christopher M. Taylor, Shane Neph, Christoph M. Koch, Saurabh Asthana, Ankit Malhotra, Ivan Adzhubei, Jason A. Greenbaum, Robert M. Andrews, Paul Flicek, Patrick J. Boyle, Hua Cao, Nigel P. Carter, Gayle K. Clelland, Sean Davis, Nathan Day, Pawandeep Dhami, Shane C. Dillon, Michael O. Dorschner, Heike Fiegler, Paul G. Giresi, Jeff Goldy, Michael Hawrylycz, Andrew Haydock, Richard Humbert, Keith D. James, Brett E. Johnson, Ericka M. Johnson, Tristan T. Frum, Elizabeth R. Rosenzweig, Neerja Karnani, Kirsten Lee, Gregory C. Lefebvre, Patrick A. Navas, Fidencio Neri, Stephen C. J. Parker, Peter J. Sabo, Richard Sandstrom, Anthony Shafer, David Vetrie, Molly Weaver, Sarah Wilcox, Man Yu, Francis S. Collins, Job Dekker, Jason D. Lieb, Thomas D. Tullius, Gregory E. Crawford, Shamil Sunyaev, William S. Noble, Ian Dunham, Anindya Dutta, Roderic Guigó, France Denoeud, Alexandre Reymond, Philipp Kapranov, Joel Rozowsky, Deyou Zheng, Robert Castelo, Adam Frankish, Jennifer Harrow, Srinka Ghosh, Albin Sandelin, Ivo L. Hofacker, Robert Baertsch, Damian Keefe, Paul Flicek, Sujit Dike, Jill Cheng, Heather A. Hirsch, Edward A. Sekinger, Julien Lagarde, Josep F. Abril, Atif Shahab, Christoph Flamm, Claudia Fried, Jörg Hackermüller, Jana Hertel, Manja Lindemeyer, Kristin Missal, Andrea Tanzer, Stefan Washietl, Jan Korbel, Olof Emanuelsson, Jakob S. Pedersen, Nancy Holroyd, Ruth Taylor, David Swarbreck, Nicholas Matthews, Mark C. Dickson, Daryl J. Thomas, Matthew T. Weirauch, James Gilbert, Jorg Drenkow, Ian Bell, XiaoDong Zhao, K.G. Srinivasan, Wing-Kin Sung, Hong Sain Ooi, Kuo Ping Chiu, Sylvain Foissac, Tyler Alioto, Michael Brent, Lior Pachter, Michael L. Tress, Alfonso Valencia, Siew Woh Choo, Chiou Yu Choo, Catherine Ucla, Caroline Manzano, Carine Wyss, Evelyn Cheung, Taane G. Clark, James B. Brown, Madhavan Ganesh, Sandeep Patel, Hari Tammana, Jacqueline Chrast, Charlotte N. Henrichsen, Chikatoshi Kai, Jun Kawai, Ugrappa Nagalakshmi, Jiaqian Wu, Zheng Lian, Jin Lian, Peter Newburger, Xueqing Zhang, Peter Bickel, John S. Mattick, Piero Carninci, Yoshihide Hayashizaki, Sherman Weissman, Emmanouil T. Dermitzakis, Elliott H. Margulies, Tim Hubbard, Richard M. Myers, Jane Rogers, Peter F. Stadler, Todd M. Lowe, Chia-Lin Wei, Yijun Ruan, Michael Snyder, Ewan Birney, Kevin Struhl, Mark Gerstein, Stylianos E. Antonarakis, Thomas R. Gingeras, James B. Brown, Paul Flicek, Yutao Fu, Damian Keefe, Ewan Birney, France Denoeud, Mark Gerstein, Eric D. Green, Philipp Kapranov, Ulaş Karaöz, Richard M. Myers, William S. Noble, Alexandre Reymond, Joel Rozowsky, Kevin Struhl, Adam Siepel, John A. Stamatoyannopoulos, Christopher M. Taylor, James Taylor, Robert E. Thurman, Thomas D. Tullius, Stefan Washietl, Deyou Zheng, Laura A. Liefer, Kris A. Wetterstrand, Peter J. Good, Elise A. Feingold, Mark S. Guyer, Francis S. Collins, Elliott H. Margulies, Gregory M. Cooper, George Asimenos, Daryl J. Thomas, Colin N. Dewey, Adam Siepel, Ewan Birney, Damian Keefe, Minmei Hou, James Taylor, Sergey Nikolaev, Juan I. Montoya-Burgos, Ari Löytynoja, Simon Whelan, Fabio Pardi, Tim Massingham, James B. Brown, Haiyan Huang, Nancy R. Zhang, Peter Bickel, Ian Holmes, James C. Mullikin, Abel Ureta-Vidal, Benedict Paten, Michael Seringhaus, Deanna Church, Kate Rosenbloom, W. James Kent, Eric A. Stone, Mark Gerstein, Stylianos E. Antonarakis, Serafim Batzoglou, Nick Goldman, Ross C. Hardison, David Haussler, Webb Miller, Lior Pachter, Eric D. Green, Arend Sidow, Zhiping Weng, Nathan D. Trinklein, Yutao Fu, Zhengdong D. Zhang, Ulaş Karaöz, Leah Barrera, Rhona Stuart, Deyou Zheng, Srinka Ghosh, Paul Flicek, David C. King, James Taylor, Adam Ameur, Stefan Enroth, Mark C. Bieda, Christoph M. Koch, Heather A. Hirsch, Chia-Lin Wei, Jill Cheng, Jonghwan Kim, Akshay A. Bhinge, Paul G. Giresi, Nan Jiang, Jun Liu, Fei Yao, Wing-Kin Sung, Kuo Ping Chiu, Vinsensius B. Vega, Charlie W.H. Lee, Patrick Ng, Atif Shahab, Edward A. Sekinger, Annie Yang, Zarmik Moqtaderi, Zhou Zhu, Xiaoqin Xu, Sharon Squazzo, Matthew J. Oberley, David Inman, Michael A. Singer, Todd A. Richmond, Kyle J. Munn, Alvaro Rada-Iglesias, Ola Wallerman, Jan Komorowski, Gayle K. Clelland, Sarah Wilcox, Shane C. Dillon, Robert M. Andrews, Joanna C. Fowler, Phillippe Couttet, Keith D. James, Gregory C. Lefebvre, Alexander W. Bruce, Oliver M. Dovey, Peter D. Ellis, Pawandeep Dhami, Cordelia F. Langford, Nigel P. Carter, David Vetrie, Philipp Kapranov, David A. Nix, Ian Bell, Sandeep Patel, Joel Rozowsky, Ghia Euskirchen, Stephen Hartman, Jin Lian, Jiaqian Wu, Alexander E. Urban, Peter Kraus, Sara Van Calcar, Nate Heintzman, Tae Hoon Kim, Kun Wang, Chunxu Qu, Gary Hon, Rosa Luna, Christopher K. Glass, M. Geoff Rosenfeld, Shelley Force Aldred, Sara J. Cooper, Anason Halees, Jane M. Lin, Hennady P. Shulha, Xiaoling Zhang, Mousheng Xu, Jaafar N. S. Haidar, Yong Yu, Ewan Birney*, Sherman Weissman, Yijun Ruan, Jason D. Lieb, Vishwanath R. Iyer, Roland D. Green, Thomas R. Gingeras, Claes Wadelius, Ian Dunham, Kevin Struhl, Ross C. Hardison, Mark Gerstein, Peggy J. Farnham, Richard M. Myers, Bing Ren, Michael Snyder, Daryl J. Thomas, Kate Rosenbloom, Rachel A. Harte, Angie S. Hinrichs, Heather Trumbower, Hiram Clawson, Jennifer Hillman-Jackson, Ann S. Zweig, Kayla Smith, Archana Thakkapallayil, Galt Barber, Robert M. Kuhn, Donna Karolchik, David Haussler, W. James Kent, Emmanouil T. Dermitzakis, Lluis Armengol, Christine P. Bird, Taane G. Clark, Gregory M. Cooper, Paul I. W. de Bakker, Andrew D. Kern, Nuria Lopez-Bigas, Joel D. Martin, Barbara E. Stranger, Daryl J. Thomas, Abigail Woodroffe, Serafim Batzoglou, Eugene Davydov, Antigone Dimas, Eduardo Eyras, Ingileif B. Hallgrímsdóttir, Ross C. Hardison, Julian Huppert, Arend Sidow, James Taylor, Heather Trumbower, Michael C. Zody, Roderic Guigó, James C. Mullikin, Gonçalo R. Abecasis, Xavier Estivill, Ewan Birney, Gerard G. Bouffard, Xiaobin Guan, Nancy F. Hansen, Jacquelyn R. Idol, Valerie V.B. Maduro, Baishali Maskeri, Jennifer C. McDowell, Morgan Park, Pamela J. Thomas, Alice C. Young, Robert W. Blakesley, Donna M. Muzny, Erica Sodergren, David A. Wheeler, Kim C. Worley, Huaiyang Jiang, George M. Weinstock, Richard A. Gibbs, Tina Graves, Robert Fulton, Elaine R. Mardis, Richard K. Wilson, Michele Clamp, James Cuff, Sante Gnerre, David B. Jaffe, Jean L. Chang, Kerstin Lindblad-Toh, Eric S. Lander, Maxim Koriabine, Mikhail Nefedov, Kazutoyo Osoegawa, Yuko Yoshinaga, Baoli Zhu, Pieter J. de Jong

ABSTRACT

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function. More... »

PAGES

799-816

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  • Journal

    TITLE

    Nature

    ISSUE

    7146

    VOLUME

    447

    Author Affiliations

  • EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
  • Department of Genome Sciences, 1705 NE Pacific Street, Box 357730, University of Washington, Seattle, Washington 98195, USA.
  • Department of Biochemistry and Molecular Genetics, Jordan 1240, Box 800733, 1300 Jefferson Park Ave, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
  • Research Group in Biomedical Informatics, Institut Municipal d'Investigació Mèdica/Universitat Pompeu Fabra, c/o Dr. Aiguader 88, Barcelona Biomedical Research Park Building, 08003 Barcelona, Catalonia, Spain.
  • Affymetrix, Inc., Santa Clara, California 95051, USA.
  • Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Biomedical Engineering Department, Boston University, 44 Cummington St., Boston, Massachusetts 02215, USA.
  • Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208114, New Haven, Connecticut 06520, USA.
  • The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
  • Division of Medical Genetics, 1705 NE Pacific Street, Box 357720, University of Washington, Seattle, Washington 98195, USA.
  • Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
  • Department of Chemistry and Program in Bioinformatics, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA.
  • Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Department of Biology and Carolina Center for Genome Sciences, CB# 3280, 202 Fordham Hall, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Allen Institute for Brain Sciences, 551 North 34th Street, Seattle, Washington 98103, USA.
  • Program in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA.
  • Institute for Genome Sciences & Policy and Department of Pediatrics, 101 Science Drive, Duke University, Durham, North Carolina 27708, USA.
  • Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
  • Genome Exploration Research Group, RIKEN Genomic Sciences Center (GSC), RIKEN Yokohama Institute, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
  • Institute for Theoretical Chemistry, University of Vienna, Währingerstraße 17, A-1090 Wien, Austria.
  • Center for Biomolecular Science and Engineering, Engineering 2, Suite 501, Mail Stop CBSE/ITI, University of California, Santa Cruz, California 95064, USA.
  • Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
  • Bioinformatics Institute, 30 Biopolis Street, #07-01 Matrix, Singapore, 138671, Singapore.
  • Department of Computer Science,, Bioinformatics Group
  • Fraunhofer Institut für Zelltherapie und Immunologie - IZI, Deutscher Platz 5e, D-04103 Leipzig, Germany.
  • Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Germany.
  • Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
  • Department of Biomolecular Engineering, University of California, Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA.
  • Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
  • Genomic Bioinformatics Program, Center for Genomic Regulation,
  • Laboratory for Computational Genomics, Washington University, Campus Box 1045, Saint Louis, Missouri 63130, USA.
  • Department of Mathematics and Computer Science, University of California, Berkeley, California 94720, USA.
  • Spanish National Cancer Research Centre, CNIO, Madrid, E-28029, Spain.
  • Department of Epidemiology and Public Health, Imperial College, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
  • Department of Applied Science & Technology, University of California, Berkeley, California 94720, USA.
  • Center for Integrative Genomics, University of Lausanne, Genopode building, 1015 Lausanne, Switzerland.
  • Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
  • Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
  • Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, Massachusetts 01605, USA.
  • Department of Statistics, University of California, Berkeley, California 94720, USA.
  • Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
  • Genome Science Laboratory, Discovery and Research Institute, RIKEN Wako Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
  • The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, New Mexico 87501, USA.
  • Program in Computational Biology & Bioinformatics, Yale University, PO Box 208114, New Haven, Connecticut 06520-8114, USA.
  • Bioinformatics Program, Boston University, 24 Cummington St., Boston, Massachusetts 02215, USA.
  • NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • †Present addresses: Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA (G.M.C.); Department of Biological Statistics & Computational Biology, Cornell University, Ithaca, New York 14853, USA (A.S.); Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK (S.W.); SwitchGear Genomics, 1455 Adams Drive, Suite 2015, Menlo Park, California 94025, USA (N.D.T.; S.F.A.).
  • Center for Comparative Genomics and Bioinformatics, Huck Institutes for Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
  • Division of Extramural Research, National Human Genome Research Institute, National Institute of Health, 5635 Fishers Lane, Suite 4076, Bethesda, Maryland 20892-9305, USA.
  • Office of the Director, National Human Genome Research Institute, National Institute of Health, 31 Center Drive, Suite 4B09, Bethesda, Maryland 20892-2152, USA.
  • Department of Computer Science, Stanford University, Stanford, California 94305, USA.
  • Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, 6720 MSC, 1300 University Ave, Madison, Wisconsin 53706, USA.
  • Department of Zoology and Animal Biology, Faculty of Sciences, University of Geneva, 1205 Geneva, Switzerland.
  • Department of Statistics, Stanford University, Stanford, California 94305, USA.
  • Department of Bioengineering, University of California, Berkeley, California 94720-1762, USA.
  • National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland 20894, USA.
  • Department of Biochemistry and Molecular Biology, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
  • Howard Hughes Medical Institute, University of California, Santa Cruz, California 95064, USA.
  • Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
  • Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
  • Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA.
  • The Linnaeus Centre for Bioinformatics, Uppsala University, BMC, Box 598, SE-75124 Uppsala, Sweden.
  • Department of Pharmacology and the Genome Center, University of California, Davis, California 95616, USA.
  • Institute for Cellular & Molecular Biology, The University of Texas at Austin, 1 University Station A4800, Austin, Texas 78712, USA.
  • NimbleGen Systems, Inc., 1 Science Court, Madison, Wisconsin 53711, USA.
  • University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
  • Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
  • University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093, USA.
  • Genes and Disease Program, Center for Genomic Regulation, c/o Dr. Aiguader 88, Barcelona Biomedical Research Park Building, 08003 Barcelona, Catalonia, Spain.
  • Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
  • Department of Biostatistics, Center for Statistical Genetics, SPH II, 1420 Washington Heights, Ann Arbor, Michigan 48109-2029, USA.
  • Department of Statistics, University of Oxford, Oxford OX1 3TG, UK.
  • Universitat Pompeu Fabra, c/o Dr. Aiguader 88, Barcelona Biomedical Research Park Building, 08003 Barcelona, Catalonia, Spain.
  • Human Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, Saint Louis, Missouri 63108, USA.
  • Broad Institute of Harvard University and Massachusetts Institute of Technology, 320 Charles Street, Cambridge, Massachusetts 02141, USA.
  • Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
  • Children's Hospital Oakland Research Institute, BACPAC Resources, 747 52nd Street, Oakland, California 94609, USA.
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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature05874

    DOI

    http://dx.doi.org/10.1038/nature05874

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1005913886

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17571346


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