Expanded encyclopaedias of DNA elements in the human and mouse genomes

ENCODE Project Consortium; Jill E Moore; Michael J Purcaro; Henry E Pratt; Charles B Epstein; Noam Shoresh; Jessika Adrian; Trupti Kawli; Carrie A Davis; Alexander Dobin; Rajinder Kaul; Jessica Halow; Eric L Van Nostrand; Peter Freese; David U Gorkin; Yin Shen; Yupeng He; Mark Mackiewicz; Florencia Pauli-Behn; Brian A Williams; Ali Mortazavi; Cheryl A Keller; Xiao-Ou Zhang; Shaimae I Elhajjajy; Jack Huey; Diane E Dickel; Valentina Snetkova; Xintao Wei; Xiaofeng Wang; Juan Carlos Rivera-Mulia; Joel Rozowsky; Jing Zhang; Surya B Chhetri; Jialing Zhang; Alec Victorsen; Kevin P White; Axel Visel; Gene W Yeo; Christopher B Burge; Eric Lécuyer; David M Gilbert; Job Dekker; John Rinn; Eric M Mendenhall; Joseph R Ecker; Manolis Kellis; Robert J Klein; William S Noble; Anshul Kundaje; Roderic Guigó; Peggy J Farnham; J Michael Cherry; Richard M Myers; Bing Ren; Brenton R Graveley; Mark B Gerstein; Len A Pennacchio; Michael P Snyder; Bradley E Bernstein; Barbara Wold; Ross C Hardison; Thomas R Gingeras; John A Stamatoyannopoulos; Zhiping Weng

doi:10.1038/s41586-020-2493-4

Expanded encyclopaedias of DNA elements in the human and mouse genomes

Nature. 2020 Jul;583(7818):699-710. doi: 10.1038/s41586-020-2493-4. Epub 2020 Jul 29.

Authors

ENCODE Project Consortium; Jill E Moore^#¹, Michael J Purcaro^#¹, Henry E Pratt^#¹, Charles B Epstein^#², Noam Shoresh^#², Jessika Adrian^#³, Trupti Kawli^#³, Carrie A Davis^#⁴, Alexander Dobin^#⁴, Rajinder Kaul^#^{5

6}, Jessica Halow^#⁵, Eric L Van Nostrand^#⁷, Peter Freese^#⁸, David U Gorkin^#^{9

10}, Yin Shen^#^{10

11}, Yupeng He^#¹², Mark Mackiewicz^#¹³, Florencia Pauli-Behn^#¹³, Brian A Williams¹⁴, Ali Mortazavi¹⁵, Cheryl A Keller¹⁶, Xiao-Ou Zhang¹, Shaimae I Elhajjajy¹, Jack Huey¹, Diane E Dickel¹⁷, Valentina Snetkova¹⁷, Xintao Wei¹⁸, Xiaofeng Wang^{19

20

21}, Juan Carlos Rivera-Mulia^{22

23}, Joel Rozowsky²⁴, Jing Zhang²⁴, Surya B Chhetri^{13

25}, Jialing Zhang²⁶, Alec Victorsen²⁷, Kevin P White²⁸, Axel Visel^{17

29

30}, Gene W Yeo⁷, Christopher B Burge³¹, Eric Lécuyer^{19

20

21}, David M Gilbert²², Job Dekker³², John Rinn³³, Eric M Mendenhall^{13

25}, Joseph R Ecker^{12

34}, Manolis Kellis^{2

35}, Robert J Klein³⁶, William S Noble³⁷, Anshul Kundaje³, Roderic Guigó³⁸, Peggy J Farnham³⁹, J Michael Cherry⁴⁰, Richard M Myers⁴¹, Bing Ren^{42

43}, Brenton R Graveley⁴⁴, Mark B Gerstein⁴⁵, Len A Pennacchio^{46

47

48}, Michael P Snyder^{49

50}, Bradley E Bernstein⁵¹, Barbara Wold⁵², Ross C Hardison⁵³, Thomas R Gingeras⁵⁴, John A Stamatoyannopoulos^{55

56

57}, Zhiping Weng^{58

59

60}

Collaborators

ENCODE Project Consortium:
Federico Abascal, Reyes Acosta, Nicholas J Addleman, Jessika Adrian, Veena Afzal, Rizi Ai, Bronwen Aken, Jennifer A Akiyama, Omar Al Jammal, Henry Amrhein, Stacie M Anderson, Gregory R Andrews, Igor Antoshechkin, Kristin G Ardlie, Joel Armstrong, Matthew Astley, Budhaditya Banerjee, Amira A Barkal, If H A Barnes, Iros Barozzi, Daniel Barrell, Gemma Barson, Daniel Bates, Ulugbek K Baymuradov, Cassandra Bazile, Michael A Beer, Samantha Beik, M A Bender, Ruth Bennett, Louis Philip Benoit Bouvrette, Bradley E Bernstein, Andrew Berry, Anand Bhaskar, Alexandra Bignell, Steven M Blue, David M Bodine, Carles Boix, Nathan Boley, Tyler Borrman, Beatrice Borsari, Alan P Boyle, Laurel A Brandsmeier, Alessandra Breschi, Emery H Bresnick, Jason A Brooks, Michael Buckley, Christopher B Burge, Rachel Byron, Eileen Cahill, Lingling Cai, Lulu Cao, Mark Carty, Rosa G Castanon, Andres Castillo, Hassan Chaib, Esther T Chan, Daniel R Chee, Sora Chee, Hao Chen, Huaming Chen, Jia-Yu Chen, Songjie Chen, J Michael Cherry, Surya B Chhetri, Jyoti S Choudhary, Jacqueline Chrast, Dongjun Chung, Declan Clarke, Neal A L Cody, Candice J Coppola, Julie Coursen, Anthony M D'Ippolito, Stephen Dalton, Cassidy Danyko, Claire Davidson, Jose Davila-Velderrain, Carrie A Davis, Job Dekker, Alden Deran, Gilberto DeSalvo, Gloria Despacio-Reyes, Colin N Dewey, Diane E Dickel, Morgan Diegel, Mark Diekhans, Vishnu Dileep, Bo Ding, Sarah Djebali, Alexander Dobin, Daniel Dominguez, Sarah Donaldson, Jorg Drenkow, Timothy R Dreszer, Yotam Drier, Michael O Duff, Douglass Dunn, Catharine Eastman, Joseph R Ecker, Matthew D Edwards, Nicole El-Ali, Shaimae I Elhajjajy, Keri Elkins, Andrew Emili, Charles B Epstein, Rachel C Evans, Iakes Ezkurdia, Kaili Fan, Peggy J Farnham, Nina P Farrell, Elise A Feingold, Anne-Maud Ferreira, Katherine Fisher-Aylor, Stephen Fitzgerald, Paul Flicek, Chuan Sheng Foo, Kevin Fortier, Adam Frankish, Peter Freese, Shaliu Fu, Xiang-Dong Fu, Yu Fu, Yoko Fukuda-Yuzawa, Mariateresa Fulciniti, Alister P W Funnell, Idan Gabdank, Timur Galeev, Mingshi Gao, Carlos Garcia Giron, Tyler H Garvin, Chelsea Anne Gelboin-Burkhart, Grigorios Georgolopoulos, Mark B Gerstein, Belinda M Giardine, David K Gifford, David M Gilbert, Daniel A Gilchrist, Shawn Gillespie, Thomas R Gingeras, Peng Gong, Alvaro Gonzalez, Jose M Gonzalez, Peter Good, Alon Goren, David U Gorkin, Brenton R Graveley, Michael Gray, Jack F Greenblatt, Ed Griffiths, Mark T Groudine, Fabian Grubert, Mengting Gu, Roderic Guigó, Hongbo Guo, Yu Guo, Yuchun Guo, Gamze Gursoy, Maria Gutierrez-Arcelus, Jessica Halow, Ross C Hardison, Matthew Hardy, Manoj Hariharan, Arif Harmanci, Anne Harrington, Jennifer L Harrow, Tatsunori B Hashimoto, Richard D Hasz, Meital Hatan, Eric Haugen, James E Hayes, Peng He, Yupeng He, Nastaran Heidari, David Hendrickson, Elisabeth F Heuston, Jason A Hilton, Benjamin C Hitz, Abigail Hochman, Cory Holgren, Lei Hou, Shuyu Hou, Yun-Hua E Hsiao, Shanna Hsu, Hui Huang, Tim J Hubbard, Jack Huey, Timothy R Hughes, Toby Hunt, Sean Ibarrientos, Robbyn Issner, Mineo Iwata, Osagie Izuogu, Tommi Jaakkola, Nader Jameel, Camden Jansen, Lixia Jiang, Peng Jiang, Audra Johnson, Rory Johnson, Irwin Jungreis, Madhura Kadaba, Maya Kasowski, Mary Kasparian, Momoe Kato, Rajinder Kaul, Trupti Kawli, Michael Kay, Judith C Keen, Sunduz Keles, Cheryl A Keller, David Kelley, Manolis Kellis, Pouya Kheradpour, Daniel Sunwook Kim, Anthony Kirilusha, Robert J Klein, Birgit Knoechel, Samantha Kuan, Michael J Kulik, Sushant Kumar, Anshul Kundaje, Tanya Kutyavin, Julien Lagarde, Bryan R Lajoie, Nicole J Lambert, John Lazar, Ah Young Lee, Donghoon Lee, Elizabeth Lee, Jin Wook Lee, Kristen Lee, Christina S Leslie, Shawn Levy, Bin Li, Hairi Li, Nan Li, Shantao Li, Xiangrui Li, Yang I Li, Ying Li, Yining Li, Yue Li, Jin Lian, Maxwell W Libbrecht, Shin Lin, Yiing Lin, Dianbo Liu, Jason Liu, Peng Liu, Tingting Liu, X Shirley Liu, Yan Liu, Yaping Liu, Maria Long, Shaoke Lou, Jane Loveland, Aiping Lu, Yuheng Lu, Eric Lécuyer, Lijia Ma, Mark Mackiewicz, Brandon J Mannion, Michael Mannstadt, Deepa Manthravadi, Georgi K Marinov, Fergal J Martin, Eugenio Mattei, Kenneth McCue, Megan McEown, Graham McVicker, Sarah K Meadows, Alex Meissner, Eric M Mendenhall, Christopher L Messer, Wouter Meuleman, Clifford Meyer, Steve Miller, Matthew G Milton, Tejaswini Mishra, Dianna E Moore, Helen M Moore, Jill E Moore, Samuel H Moore, Jennifer Moran, Ali Mortazavi, Jonathan M Mudge, Nikhil Munshi, Rabi Murad, Richard M Myers, Vivek Nandakumar, Preetha Nandi, Anil M Narasimha, Aditi K Narayanan, Hannah Naughton, Fabio C P Navarro, Patrick Navas, Jurijs Nazarovs, Jemma Nelson, Shane Neph, Fidencio Jun Neri, Joseph R Nery, Amy R Nesmith, J Scott Newberry, Kimberly M Newberry, Vu Ngo, Rosy Nguyen, Thai B Nguyen, Tung Nguyen, Andrew Nishida, William S Noble, Catherine S Novak, Eva Maria Novoa, Briana Nuñez, Charles W O'Donnell, Sara Olson, Kathrina C Onate, Ericka Otterman, Hakan Ozadam, Michael Pagan, Tsultrim Palden, Xinghua Pan, Yongjin Park, E Christopher Partridge, Benedict Paten, Florencia Pauli-Behn, Michael J Pazin, Baikang Pei, Len A Pennacchio, Alexander R Perez, Emily H Perry, Dmitri D Pervouchine, Nishigandha N Phalke, Quan Pham, Doug H Phanstiel, Ingrid Plajzer-Frick, Gabriel A Pratt, Henry E Pratt, Sebastian Preissl, Jonathan K Pritchard, Yuri Pritykin, Michael J Purcaro, Qian Qin, Giovanni Quinones-Valdez, Ines Rabano, Ernest Radovani, Anil Raj, Nisha Rajagopal, Oren Ram, Lucia Ramirez, Ricardo N Ramirez, Dylan Rausch, Soumya Raychaudhuri, Joseph Raymond, Rozita Razavi, Timothy E Reddy, Thomas M Reimonn, Bing Ren, Alexandre Reymond, Alex Reynolds, Suhn K Rhie, John Rinn, Miguel Rivera, Juan Carlos Rivera-Mulia, Brian S Roberts, Jose Manuel Rodriguez, Joel Rozowsky, Russell Ryan, Eric Rynes, Denis N Salins, Richard Sandstrom, Takayo Sasaki, Shashank Sathe, Daniel Savic, Alexandra Scavelli, Jonathan Scheiman, Christoph Schlaffner, Jeffery A Schloss, Frank W Schmitges, Lei Hoon See, Anurag Sethi, Manu Setty, Anthony Shafer, Shuo Shan, Eilon Sharon, Quan Shen, Yin Shen, Richard I Sherwood, Minyi Shi, Sunyoung Shin, Noam Shoresh, Kyle Siebenthall, Cristina Sisu, Teri Slifer, Cricket A Sloan, Anna Smith, Valentina Snetkova, Michael P Snyder, Damek V Spacek, Sharanya Srinivasan, Rohith Srivas, George Stamatoyannopoulos, John A Stamatoyannopoulos, Rebecca Stanton, Dave Steffan, Sandra Stehling-Sun, J Seth Strattan, Amanda Su, Balaji Sundararaman, Marie-Marthe Suner, Tahin Syed, Matt Szynkarek, Forrest Y Tanaka, Danielle Tenen, Mingxiang Teng, Jeffrey A Thomas, Dave Toffey, Michael L Tress, Diane E Trout, Gosia Trynka, Junko Tsuji, Sean A Upchurch, Oana Ursu, Barbara Uszczynska-Ratajczak, Mia C Uziel, Alfonso Valencia, Benjamin Van Biber, Arjan G van der Velde, Eric L Van Nostrand, Yekaterina Vaydylevich, Jesus Vazquez, Alec Victorsen, Jost Vielmetter, Jeff Vierstra, Axel Visel, Anna Vlasova, Christopher M Vockley, Simona Volpi, Shinny Vong, Hao Wang, Mengchi Wang, Qin Wang, Ruth Wang, Tao Wang, Wei Wang, Xiaofeng Wang, Yanli Wang, Nathaniel K Watson, Xintao Wei, Zhijie Wei, Hendrik Weisser, Sherman M Weissman, Rene Welch, Robert E Welikson, Zhiping Weng, Harm-Jan Westra, John W Whitaker, Collin White, Kevin P White, Andre Wildberg, Brian A Williams, David Wine, Heather N Witt, Barbara Wold, Maxim Wolf, James Wright, Rui Xiao, Xinshu Xiao, Jie Xu, Jinrui Xu, Koon-Kiu Yan, Yongqi Yan, Hongbo Yang, Xinqiong Yang, Yi-Wen Yang, Galip Gürkan Yardımcı, Brian A Yee, Gene W Yeo, Taylor Young, Tianxiong Yu, Feng Yue, Chris Zaleski, Chongzhi Zang, Haoyang Zeng, Weihua Zeng, Daniel R Zerbino, Jie Zhai, Lijun Zhan, Ye Zhan, Bo Zhang, Jialing Zhang, Jing Zhang, Kai Zhang, Lijun Zhang, Peng Zhang, Qi Zhang, Xiao-Ou Zhang, Yanxiao Zhang, Zhizhuo Zhang, Yuan Zhao, Ye Zheng, Guoqing Zhong, Xiao-Qiao Zhou, Yun Zhu, Jared Zimmerman

Affiliations

¹ University of Massachusetts Medical School, Program in Bioinformatics and Integrative Biology, Worcester, MA, USA.
² The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
³ Department of Genetics, School of Medicine, Stanford University, Palo Alto, CA, USA.
⁴ Cold Spring Harbor Laboratory, Functional Genomics, Cold Spring Harbor, NY, USA.
⁵ Altius Institute for Biomedical Sciences, Seattle, WA, USA.
⁶ Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
⁷ Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, Stem Cell Program, Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
⁸ Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁹ Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
¹⁰ Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA, USA.
¹¹ Institute for Human Genetics, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
¹² Genomics Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
¹³ HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
¹⁴ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
¹⁵ Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA, USA.
¹⁶ Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
¹⁷ Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
¹⁸ Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT, USA.
¹⁹ Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, Quebec, Canada.
²⁰ Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
²¹ Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Quebec, Canada.
²² Department of Biological Science, Florida State University, Tallahassee, FL, USA.
²³ Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN, USA.
²⁴ Yale University, New Haven, CT, USA.
²⁵ Biological Sciences, University of Alabama in Huntsville, Huntsville, AL, USA.
²⁶ Department of Genetics, School of Medicine, Yale University, New Haven, CT, USA.
²⁷ Department of Human Genetics, Institute for Genomics and Systems Biology, The University of Chicago, Chicago, IL, USA.
²⁸ Tempus Labs, Chicago, IL, USA.
²⁹ US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
³⁰ School of Natural Sciences, University of California, Merced, Merced, CA, USA.
³¹ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
³² HHMI and Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA, USA.
³³ University of Colorado Boulder, Boulder, CO, USA.
³⁴ Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA.
³⁵ Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
³⁶ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³⁷ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
³⁸ Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology and Universitat Pompeu Fabra, Barcelona, Spain.
³⁹ Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴⁰ Department of Genetics, School of Medicine, Stanford University, Palo Alto, CA, USA. cherry@stanford.edu.
⁴¹ HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA. rmyers@hudsonalpha.org.
⁴² Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA. biren@ucsd.edu.
⁴³ Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA, USA. biren@ucsd.edu.
⁴⁴ Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT, USA. graveley@uchc.edu.
⁴⁵ Yale University, New Haven, CT, USA. mark@gersteinlab.org.
⁴⁶ Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. lapennacchio@lbl.gov.
⁴⁷ US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. lapennacchio@lbl.gov.
⁴⁸ Comparative Biochemistry Program, University of California, Berkeley, CA, USA. lapennacchio@lbl.gov.
⁴⁹ Department of Genetics, School of Medicine, Stanford University, Palo Alto, CA, USA. mpsnyder@stanford.edu.
⁵⁰ Cardiovascular Institute, Stanford School of Medicine, Stanford, CA, USA. mpsnyder@stanford.edu.
⁵¹ Broad Institute and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Bernstein.Bradley@mgh.harvard.edu.
⁵² Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. woldb@caltech.edu.
⁵³ Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA. rch8@psu.edu.
⁵⁴ Cold Spring Harbor Laboratory, Functional Genomics, Cold Spring Harbor, NY, USA. gingeras@cshl.edu.
⁵⁵ Altius Institute for Biomedical Sciences, Seattle, WA, USA. jstam@altius.org.
⁵⁶ Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. jstam@altius.org.
⁵⁷ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA. jstam@altius.org.
⁵⁸ University of Massachusetts Medical School, Program in Bioinformatics and Integrative Biology, Worcester, MA, USA. zhiping.weng@umassmed.edu.
⁵⁹ Department of Thoracic Surgery, Clinical Translational Research Center, Shanghai Pulmonary Hospital, The School of Life Sciences and Technology, Tongji University, Shanghai, China. zhiping.weng@umassmed.edu.
⁶⁰ Bioinformatics Program, Boston University, Boston, MA, USA. zhiping.weng@umassmed.edu.

^# Contributed equally.

Abstract

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE¹ and Roadmap Epigenomics² data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Chromatin / genetics
Chromatin / metabolism
DNA / chemistry
DNA / genetics*
DNA Footprinting
DNA Methylation / genetics
DNA Replication Timing
Databases, Genetic*
Deoxyribonuclease I / metabolism
Genome / genetics*
Genome, Human
Genomics*
Histones / metabolism
Humans
Mice
Mice, Transgenic
Molecular Sequence Annotation*
RNA-Binding Proteins / genetics
Registries*
Regulatory Sequences, Nucleic Acid / genetics*
Transcription, Genetic / genetics
Transposases / metabolism

Substances

Chromatin
Histones
RNA-Binding Proteins
DNA
Transposases
Deoxyribonuclease I

Abstract

Publication types

MeSH terms

Substances

Grants and funding