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Spatiotemporal DNA methylome dynamics of the developing mouse fetus

He, Yupeng and Hariharan, Manoj and Gorkin, David U. and Dickel, Diane E. and Luo, Chongyuan and Castanon, Rosa G. and Nery, Joseph R. and Lee, Ah Young and Zhao, Yuan and Huang, Hui and Williams, Brian A. and Trout, Diane and Amrhein, Henry and Fang, Rongxin and Chen, Huaming and Li, Bin and Visel, Axel and Pennacchio, Len A. and Ren, Bing and Ecker, Joseph R. (2020) Spatiotemporal DNA methylome dynamics of the developing mouse fetus. Nature, 583 (7818). pp. 752-759. ISSN 0028-0836. https://resolver.caltech.edu/CaltechAUTHORS:20181101-114159969

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Abstract

Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41586-020-2119-xDOIArticle
https://doi.org/10.1101/166744DOIDiscussion Paper
ORCID:
AuthorORCID
He, Yupeng0000-0002-8319-0510
Hariharan, Manoj0000-0002-1006-5372
Gorkin, David U.0000-0003-4944-4107
Dickel, Diane E.0000-0001-5497-6824
Luo, Chongyuan0000-0002-8541-0695
Castanon, Rosa G.0000-0003-1791-002X
Nery, Joseph R.0000-0003-0153-5659
Amrhein, Henry0000-0002-4264-140X
Fang, Rongxin0000-0001-8746-9650
Chen, Huaming0000-0001-5289-7882
Visel, Axel0000-0002-4130-7784
Pennacchio, Len A.0000-0002-8748-3732
Ren, Bing0000-0002-2829-1554
Ecker, Joseph R.0000-0001-5799-5895
Alternate Title:Spatiotemporal DNA Methylome Dynamics of the Developing Mammalian Fetus
Additional Information:© 2020 the Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 09 August 2017; Accepted 11 June 2019; Published 29 July 2020. We thank J. Li, S. C. Huang, E. A. Mukamel and L. Song for critical comments. D.U.G. is supported by the A.P. Giannini Foundation and NIH IRACDA K12 GM068524. A.V. and L.A.P. were supported by National Institutes of Health grant U54HG006997, and the research conducted at the E. O. Lawrence Berkeley National Laboratory was performed under Department of Energy Contract DE-AC02-05CH11231, University of California. J.R.E. is an Investigator of the Howard Hughes Medical Institute. Use of the Extreme Science and Engineering Discovery Environment (XSEDE) was supported by National Science Foundation grant number ACI-1548562. This work was supported by the National Institutes of Health ENCODE Project (U54 HG006997). The data that support these findings are publicly accessible at https://www.encodeproject.org/ and http://neomorph.salk.edu/ENCODE_mouse_fetal_development.html. Additional RNA-seq data sets are available at the NCBI Gene Expression Omnibus (accession GSE100685). Further details describing the data used in this study can be found in Supplementary Tables 1 and 2. Author Contributions: Y.H., M.H., Y.Z., R.F., H.C. and B.L. performed data analysis. Y.H. and M.H. wrote the manuscript. Y.H., M.H., C.L. and J.R.E. edited the manuscript. D.E.D., A.V. and the L.A.P. group collected the tissues from mouse embryo for epigenome and transcriptome profiling. D.U.G., A.Y.L. and B.R. generated the histone modification data. Y.Z., H.H. and B.R. generated the ATAC–seq data. B.A.W., D.T. and H.A. generated RNA-seq data. J.R.N. and R.G.C. generated the WGBS data and the validation set of RNA-seq data. J.R.E. supervised the project. Competing interests: B.R. is a co-founder and shareholder of Arima Genomics, Inc. The other authors declare no competing interests.
Funders:
Funding AgencyGrant Number
A. P. Giannini FoundationUNSPECIFIED
NIHIRACDA K12 GM068524
NIHU54HG006997
Department of Energy (DOE)DE-AC02-05CH11231
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NSFACI-1548562
NIHU54 HG006997
Subject Keywords:DNA methylation; Epigenomics; Gene regulation
Issue or Number:7818
Record Number:CaltechAUTHORS:20181101-114159969
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20181101-114159969
Official Citation:He, Y., Hariharan, M., Gorkin, D.U. et al. Spatiotemporal DNA methylome dynamics of the developing mouse fetus. Nature 583, 752–759 (2020). https://doi.org/10.1038/s41586-020-2119-x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90568
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:01 Nov 2018 19:48
Last Modified:03 Aug 2020 16:45

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