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Published November 20, 2014 | Supplemental Material + Published
Journal Article Open

A comparative encyclopedia of DNA elements in the mouse genome


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.

Additional Information

© 2014 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution- NonCommercial-ShareAlike 3.0 Unported licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-sa/3.0. Received 3 February; accepted 24 October 2014. Published online 19 November 2014. This work is funded by grants R01HG003991 (B.R.), 1U54HG007004 (T.R.G.), 3RC2HG005602 (M.P.S.), GM083337 and GM085354 (D.M.G.), F31CA165863 (B.D.P.), RC2HG005573 and R01DK065806 (R.C.H.) from the National Institutes of Health, and BIO2011-26205 from the Spanish Plan Nacional and ERC 294653 (to R.G.). J.V. is supported by a National Science Foundation Graduate Research Fellowship under grant no. DGE-071824. K.B., M.P., J.H. and P.F. acknowledge the Wellcome Trust (grant number 095908), the NHGRI (grant number U01HG004695) and the European Molecular Biology Laboratory. We thank G. Hon for helping the analysis of high-throughput enhancer validation. L.S. is supported by R01HD043997-09. S.L. was supported by grants F32HL110473 and K99HL119617. Author Contributions: F.Y., Y.C., A.B., J.V., W.W., T.R., M.A. Beer, R.C.H., J.A.S., M.P.S., R.G., T.R.G., D.M.G. and B.R. led the data analysis effort, R. Sandstrom, Z.M., C.D., B.D.P., Y.S., R.C.H., J.A.S., M.P.S., R.G., T.R.G., D.M.G. and B.R. led the data production. F.Y., M.A. Beer, L.E., Y.C., P.C., A.B., A.K., S.L., Y.L., J.V., R. Sandstrom, R.E.T., E.R., E.H., A.P.R., S.N., R.H., W.W., T.M., R.S.H., C.J., A.M., B.D.P., T.R., T.K., D. Lee, O.D., J.T., C.Z., A.D., D.D.P., S.D., P.P., J. Lagarde, G.B., A.T., K.B., M.P., P.F. and J.H. analysed data. Y.S., D.M., L.P., Z.Y., S.K., Z.M., T.K., G.E., J. Lian, S.M.W., R.K., M.A. Bender, S.L., Y.L., M.Z., R.B., M.T.G., A.J., S.V., K.L., D.B., F.N., M.D., T.C., R.S.H., P.J.S., M.S.W., T.A.R., E.G., A.S., T.K., E.H., D.D., M.D.B., L.S., A.R., S.J., R. Samstein, E.E.E., S.H.O., D. Levasseur, T.P., K.-H.C., A.S., C.D., P.T., W.W., C.A.K., C.S.M., T.M., D.J., N.D., B.D.P., T.R., C.D., L.-H.S., M.F., J.D. produced data. F.Y., Y.C., W.W., T.R., B.D.P., S.L., Y.L., C.J., C.D., A.D., A.B., D.D.P., S.D., C.N., A.M., J.A.S., M.P.S., R.G., T.R.G., D.M.G., R.C.H., M.A. Beer., B.R. wrote the manuscript. The role of the NHGRI Project Management Group (P.J.G., R.F.L., L.B.A., X.-Q.Z., M.J.P., E.A.F.) in the preparation of this paper was limited to coordination and scientific management of the Mouse ENCODE consortium.

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