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Spatiotemporal DNA methylome dynamics of the developing mouse fetus

Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited(1,2). Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at...

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Autores principales: He, Yupeng, Hariharan, Manoj, Gorkin, David U., Dickel, Diane E., Luo, Chongyuan, Castanon, Rosa G., Nery, Joseph R., Lee, Ah Young, Zhao, Yuan, Huang, Hui, Williams, Brian A., Trout, Diane, Amrhein, Henry, Fang, Rongxin, Chen, Huaming, Li, Bin, Visel, Axel, Pennacchio, Len A., Ren, Bing, Ecker, Joseph R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398276/
https://www.ncbi.nlm.nih.gov/pubmed/32728242
http://dx.doi.org/10.1038/s41586-020-2119-x
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author He, Yupeng
Hariharan, Manoj
Gorkin, David U.
Dickel, Diane E.
Luo, Chongyuan
Castanon, Rosa G.
Nery, Joseph R.
Lee, Ah Young
Zhao, Yuan
Huang, Hui
Williams, Brian A.
Trout, Diane
Amrhein, Henry
Fang, Rongxin
Chen, Huaming
Li, Bin
Visel, Axel
Pennacchio, Len A.
Ren, Bing
Ecker, Joseph R.
author_facet He, Yupeng
Hariharan, Manoj
Gorkin, David U.
Dickel, Diane E.
Luo, Chongyuan
Castanon, Rosa G.
Nery, Joseph R.
Lee, Ah Young
Zhao, Yuan
Huang, Hui
Williams, Brian A.
Trout, Diane
Amrhein, Henry
Fang, Rongxin
Chen, Huaming
Li, Bin
Visel, Axel
Pennacchio, Len A.
Ren, Bing
Ecker, Joseph R.
author_sort He, Yupeng
collection PubMed
description Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited(1,2). 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.
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spelling pubmed-73982762020-08-17 Spatiotemporal DNA methylome dynamics of the developing mouse fetus He, Yupeng Hariharan, Manoj Gorkin, David U. Dickel, Diane E. Luo, Chongyuan Castanon, Rosa G. Nery, Joseph R. Lee, Ah Young Zhao, Yuan Huang, Hui Williams, Brian A. Trout, Diane Amrhein, Henry Fang, Rongxin Chen, Huaming Li, Bin Visel, Axel Pennacchio, Len A. Ren, Bing Ecker, Joseph R. Nature Article Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited(1,2). 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. Nature Publishing Group UK 2020-07-29 2020 /pmc/articles/PMC7398276/ /pubmed/32728242 http://dx.doi.org/10.1038/s41586-020-2119-x Text en © The Author(s) 2020 Open Access 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/.
spellingShingle Article
He, Yupeng
Hariharan, Manoj
Gorkin, David U.
Dickel, Diane E.
Luo, Chongyuan
Castanon, Rosa G.
Nery, Joseph R.
Lee, Ah Young
Zhao, Yuan
Huang, Hui
Williams, Brian A.
Trout, Diane
Amrhein, Henry
Fang, Rongxin
Chen, Huaming
Li, Bin
Visel, Axel
Pennacchio, Len A.
Ren, Bing
Ecker, Joseph R.
Spatiotemporal DNA methylome dynamics of the developing mouse fetus
title Spatiotemporal DNA methylome dynamics of the developing mouse fetus
title_full Spatiotemporal DNA methylome dynamics of the developing mouse fetus
title_fullStr Spatiotemporal DNA methylome dynamics of the developing mouse fetus
title_full_unstemmed Spatiotemporal DNA methylome dynamics of the developing mouse fetus
title_short Spatiotemporal DNA methylome dynamics of the developing mouse fetus
title_sort spatiotemporal dna methylome dynamics of the developing mouse fetus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398276/
https://www.ncbi.nlm.nih.gov/pubmed/32728242
http://dx.doi.org/10.1038/s41586-020-2119-x
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