Joshua W. K. Ho1,2*†, Youngsook L. Jung1,2*, Tao Liu3,4*†, Burak H. Alver1, Soohyun Lee1, Kohta Ikegami5†, Kyung-Ah Sohn6,7, Aki Minoda8,9†, Michael Y. Tolstorukov1,2,10, Alex Appert11, Stephen C. J. Parker12,13, Tingting Gu14, Anshul Kundaje15,16†, Nicole C. Riddle14†, Eric Bishop1,17, Thea A. Egelhofer18, Sheng’en Shawn Hu19, Artyom A. Alekseyenko2,20, Andreas Rechtsteiner18, Dalal Asker21,22, Jason A. Belsky23, Sarah K. Bowman10, Q. Brent Chen5, Ron A.-J. Chen11,Daniel S. Day1,24, Yan Dong11, ndrea C. Dose25, Xikun Duan19, Charles B. Epstein16, Sevinc Ercan5,26, Elise A. Feingold13, Francesco Ferrari1, Jacob M. Garrigues18, Nils Gehlenborg1,16, Peter J. Good13, Psalm Haseley1,2, Daniel He9, Moritz Herrmann11,Michael M. Hoffman27, Tess E. Jeffers5†, Peter V. Kharchenko1, Paulina Kolasinska-Zwierz11, Chitra V. Kotwaliwale9,28, Nischay Kumar15,16, Sasha A. Langley8,9, Erica N. Larschan29, Isabel Latorre11, Maxwell W. Libbrecht30, Xueqiu Lin19, Richard Park1,17, Michael J. Pazin13, Hoang N. Pham8,9,28, Annette Plachetka2,20, Bo Qin19, Yuri B. Schwartz21,31, NoamShoresh16, Przemyslaw Stempor11, Anne Vielle11, Chengyang Wang19, Christina M. Whittle9,28, Huiling Xue1,2, Robert E. Kingston10, Ju Han Kim7,32, Bradley E. Bernstein16,28,33, Abby F. Dernburg8,9,28, Vincenzo Pirrotta21, Mitzi I. Kuroda2,20,WilliamS. Noble30,34, Thomas D. Tullius17,35, Manolis Kellis15,16, David M. MacAlpine23, Susan Strome18, Sarah C. R. Elgin14, Xiaole Shirley Liu3,4,16, Jason D. Lieb5†, Julie Ahringer11, Gary H. Karpen8,9 & Peter J. Park1,2,36
1Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA. 2Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 3Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 4Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 450 Brookline Avenue, Boston, Massachusetts 02215, USA. 5Department of Biology and Carolina Center for GenomeSciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. 6Department of Information and Computer Engineering, Ajou University, Suwon 443-749, Korea. 7Systems Biomedical Informatics Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea. 8Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA. 9Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA. 10Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. 11The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. 12National Institute of General Medical Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA. 13National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. 14Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA. 15Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. 16Broad Institute, Cambridge, Massachusetts 02141, USA. 17Program in Bioinformatics, Boston University, Boston, Massachusetts 02215, USA. 18Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA. 19Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China. 20Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. 21Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NewJersey 08854, USA. 22Food Science and Technology Department, Faculty of Agriculture, Alexandria University,21545El-Shatby, Alexandria, Egypt. 23Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. 24Harvard/MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA. 25Department of Anatomy Physiology and Cell Biology, University of California Davis, Davis, California 95616, USA. 26Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York 10003, USA. 27Princess Margaret Cancer Centre, Toronto, Ontario M6G 1L7, Canada. 28Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. 29Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA. 30Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA. 31Department of Molecular Biology, Umea University, 901 87 Umea, Sweden. 32Seoul National University Biomedical Informatics, Division of Biomedical Informatics, College of Medicine, Seoul National University, Seoul 110-799, Korea. 33Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. 34Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. 35Department of Chemistry, Boston University, Boston, Massachusetts 02215, USA. 36Informatics Program, Children’s Hospital, Boston, Massachusetts 02215, USA. †Present addresses: Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.).
*These authors contributed equally to this work.
Correspondence to: David M. MacAlpine or Susan Strome or Sarah C. R. Elgin or Xiaole Shirley Liu or Jason D. Lieb or Julie Ahringer or Gary H. Karpen or Peter J. Park
Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms1, 2, 3. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal ‘arms’, and centromeres distributed along their lengths4, 5. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.