A comparative encyclopedia of DNA elements in the mouse genome
Open accessAbstract
The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases. The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. The mouse is the premier model organism in biomedical research. To gain greater insights into the shared and species-specific transcriptional and cellular regulatory programs, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. These finding are compared with the corresponding human data to confirm substantial conservation in the newly annotated potential functional sequences, and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. The data and their analyses provide a valuable resource for research into mammalian biology and mechanisms of human diseases.
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Large consortia projects (GTEx, Epigenome Roadmap, ENCODE) are already generating data from multiple-omics levels that facilitate integrated analyses.
“Projects from large consortia like GTEx [156], the Epigenome Roadmap [176] and ENCODE [15] are already generating data from multiple-omics levels that facilitate these integrated analyses.”
From Gene co-expression analysis for functional classification and gene–disease predictions (2017) · cites this paper as [15]
HDAC1 profile in TgSpi1 cells proportionally colocalized with SIN3A profile but not with P300 profile.
“Notably, the HDAC1 profile in TgSpi1 erythroleukaemic cells proportionally colocalized with the SIN3A profile but not with the histone acetylase P300 (previously published datasets, (56)) profile in erythroleukaemic cells (Supplementary Figure S5H)”
From HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependent gene repression in murine erythroleukaemia (2022) · cites this paper as [56]
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An atlas of gene regulatory elements in adult mouse cerebrum
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A quantitative framework for characterizing the evolutionary history of mammalian gene expression
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The Molecular Basis of Human Brain Evolution
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An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum
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Self-citationWhere next for the reproducibility agenda in computational biology?
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Dissecting the Genetic Architecture of Cystatin C in Diversity Outbred Mice
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“Normalization and differential analyses were performed with EdgeR (version 3.36.0; Robinson et al , 2010; Liu et al , 2015; options: lowly expressed genes filtered out, cutoff: < 1 CPM in n samples — with n corresponding to number of biological replicates in one condition, FDR < 0.15, normalization…”
Influential
- Authors
- Yue, F., Cheng, Y., Breschi, A., Vierstra, J., Wu, W., Ryba, T., Sandstrom, R., Ma, Z., Davis, C., Pope, B. D., Shen, Y., Pervouchine, D. D., Djebali, S., Thurman, R. E., Kaul, R., Rynes, E., Kirilusha, A., Marinov, G. K., Williams, B. A., Trout, D., Amrhein, H., Fisher-Aylor, K., Antoshechkin, I., DeSalvo, G., See, L.-H., Fastuca, M., Drenkow, J., Zaleski, C., Dobin, A., Prieto, P., Lagarde, J., Bussotti, G., Tanzer, A., Denas, O., Li, K., Bender, M. A., Zhang, M., Byron, R., Groudine, M. T., McCleary, D., Pham, L., Ye, Z., Kuan, S., Edsall, L., Wu, Y.-C., Rasmussen, M. D., Bansal, M. S., Kellis, M., Keller, C. A., Morrissey, C. S., Mishra, T., Jain, D., Dogan, N., Harris, R. S., Cayting, P., Kawli, T., Boyle, A. P., Euskirchen, G., Kundaje, A., Lin, S., Lin, Y., Jansen, C., Malladi, V. S., Cline, M. S., Erickson, D. T., Kirkup, V. M., Learned, K., Sloan, C. A., Rosenbloom, K. R., Lacerda de Sousa, B., Beal, K., Pignatelli, M., Flicek, P., Lian, J., Kahveci, T., Lee, D., James Kent, W., Ramalho Santos, M., Herrero, J., Notredame, C., Johnson, A., Vong, S., Lee, K., Bates, D., Neri, F., Diegel, M., Canfield, T., Sabo, P. J., Wilken, M. S., Reh, T. A., Giste, E., Shafer, A., Kutyavin, T., Haugen, E., Dunn, D., Reynolds, A. P., Neph, S., Humbert, R., Scott Hansen, R., De Bruijn, M., Selleri, L., Rudensky, A., Josefowicz, S., Samstein, R., Eichler, E. E., Orkin, S. H., Levasseur, D., Papayannopoulou, T., Chang, K.-H., Skoultchi, A., Gosh, S., Disteche, C., Treuting, P., Wang, Y., Weiss, M. J., Blobel, G. A., Cao, X., Zhong, S., Wang, T., Good, P. J., Lowdon, R. F., Adams, L. B., Zhou, X.-Q., Pazin, M. J., Feingold, E. A., Wold, B., Taylor, J., Mortazavi, A., Weissman, S. M., Stamatoyannopoulos, J. A., Snyder, M. P., Guigo, R., Gingeras, T. R., Gilbert, D. M., Hardison, R. C., Beer, M. A., Ren, B., & The Mouse ENCODE Consortium
- Affiliations
- Pennsylvania State University (US)
- Stanford University (US)
- Universitat Pompeu Fabra (ES)
- University of Washington (US)
- Florida State University (US)
- Cold Spring Harbor Laboratory (US)
- University of California San Diego (US)
- California Institute of Technology (US)
- Emory University (US)
- Fred Hutch Cancer Center (US)
- MIT Computer Science and Artificial Intelligence Laboratory (US)
- Broad Institute (US)
- University of California, Irvine (US)
- University of California, Santa Cruz (US)
- European Bioinformatics Institute (GB)
- Yale University (US)
- University of Florida (US)
- Johns Hopkins University (US)
- Weill Cornell Medicine (US)
- Memorial Sloan Kettering Cancer Center (US)
- Harvard University (US)
- University of Iowa (US)
- Albert Einstein College of Medicine (US)
- St. Jude Children's Research Hospital (US)
- Children's Hospital of Philadelphia (US)
- Washington University in St. Louis (US)
- National Institutes of Health (US)
- Corresponding author
- Stamatoyannopoulos, John A.
- Snyder, Michael P.
- Gingeras, Thomas R.
- Gilbert, David M.
- Hardison, Ross C.
- Beer, Michael A.
- Ren, Bing
- ORCID
- Yue, Feng
- Cheng, Yong
- Breschi, Alessandra
- Vierstra, Jeff
- Ryba, Tyrone
- Sandstrom, Richard
- Pope, Benjamin D.
- Pervouchine, Dmitri D.
- Djebali, Sarah
- Kaul, Rajinder
- Rynes, Eric
- Marinov, Georgi K.
- Williams, Brian A.
- Trout, Diane
- Amrhein, Henry
- Fisher-Aylor, Katherine
- Antoshechkin, Igor
- DeSalvo, Gilberto
- Prieto, Pablo
- Lagarde, Julien
- Bussotti, Giovanni
- Zhang, Miaohua
- Groudine, Mark T.
- Ye, Zhen
- Kuan, Samantha
- Edsall, Lee
- Wu, Yi-Chieh
- Bansal, Mukul S.
- Kellis, Manolis
- Keller, Cheryl A.
- Morrissey, Christapher S.
- Mishra, Tejaswini
- Jain, Deepti
- Boyle, Alan P.
- Kundaje, Anshul
- Lin, Shin
- Lin, Yiing
- Jansen, Camden
- Malladi, Venkat S.
- Cline, Melissa S.
- Learned, Katrina
- Sloan, Cricket A.
- Rosenbloom, Kate R.
- Beal, Kathryn
- Pignatelli, Miguel
- Flicek, Paul
- Kahveci, Tamer
- Lee, Dongwon
- Herrero, Javier
- Lee, Kristen
- Bates, Daniel
- Sabo, Peter J.
- Reh, Thomas A.
- Haugen, Eric
- Reynolds, Alex P.
- Neph, Shane
- Selleri, Licia
- Rudensky, Alexander
- Josefowicz, Steven
- Samstein, Robert
- Eichler, Evan E.
- Orkin, Stuart H.
- Papayannopoulou, Thalia
- Skoultchi, Arthur
- Treuting, Piper
- Wang, Yanli
- Weiss, Mitchell J.
- Blobel, Gerd A.
- Cao, Xiaoyi
- Zhong, Sheng
- Wang, Ting
- Lowdon, Rebecca F.
- Adams, Leslie B.
- Pazin, Michael J.
- Wold, Barbara
- Taylor, James
- Mortazavi, Ali
- Stamatoyannopoulos, John A.
- Snyder, Michael P.
- Gingeras, Thomas R.
- Gilbert, David M.
- Hardison, Ross C.
- Beer, Michael A.
- Ren, Bing
- Venue
- Nature
- Published
- 2014-11-19
- Volume
- 515
- Issue
- 7527
- Pages
- 355-364
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4266106
- OpenAlex
- W1991543373
- Cited by
- 1,781
- References
- 75
- Citations by year
- 2026: 64 · 2025: 110 · 2024: 177 · 2023: 156 · 2022: 154 · 2021: 174 · 2020: 211 · 2019: 201 · 2018: 178 · 2017: 134 · 2016: 117 · 2015: 96 · 2014: 9
- FWCI
- 48.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by-nc-sa)
- Funders
- National Science Foundation (DGE-071824)
- Howard Hughes Medical Institute
- Wellcome Trust (095908, 26205)
- European Molecular Biology Laboratory
- National Institutes of Health (GM085354, 5p30ca045508-35)
- National Heart, Lung, and Blood Institute (U01HL099993, P01HL110860, U01HL099656, K99HL119617, P01HL064190, F32HL110473)
- National Human Genome Research Institute (U54HG007004, U54HG006997, R01HG007175, U01HG004695, RC2HG005602, K99HG007356, R01HG007354, RC2HG005573, R01HG003991, R01HG007348, R01HG004037, U54HG006998)
- National Eye Institute (R01EY021482)
- National Cancer Institute (F31CA165863, P30-CA045508, P30CA008748)
- National Institute of General Medical Sciences (GM083337, T32GM081739, P01GM085354, GM085354, R01GM083337)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK096266, R01DK065806, R56DK065806, R37DK044746)
- National Institute of Environmental Health Sciences (R01ES024992)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD043997)
- FP7 Ideas: European Research Council (294653)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- mouse genome, DNA regulatory elements, transcription factor binding, DNase I hypersensitivity, chromatin modification, replication domains, chromatin organization, human-mouse sequence conservation, transcriptional regulation, functional genomic annotation
- MeSH terms
- Animals, Chromatin, Deoxyribonuclease I, DNA Replication, Gene Expression Regulation, Humans, Regulatory Sequences, Nucleic Acid, RNA, Species Specificity, Transcription Factors, Genome, Conserved Sequence, Cell Lineage, Genomics, Mice, Gene Regulatory Networks, Genome-Wide Association Study, Molecular Sequence Annotation, Transcriptome
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