Spatiotemporal DNA methylome dynamics of the developing mouse fetus

Yupeng He, Manoj Hariharan, David U. Gorkin, Diane E. Dickel, Chongyuan Luo, Rosa G. Castanon, Joseph R. Nery, Ah Young Lee, Yuan Zhao, Hui Huang, Brian A. Williams, Diane Trout, Henry Amrhein, Rongxin Fang, Huaming Chen, Bin Li, Axel Visel, Len A. Pennacchio, Bing Ren and Joseph R. Ecker ()
Additional contact information
Yupeng He: The Salk Institute for Biological Studies
Manoj Hariharan: The Salk Institute for Biological Studies
David U. Gorkin: University of California, San Diego
Diane E. Dickel: Lawrence Berkeley National Laboratory
Chongyuan Luo: The Salk Institute for Biological Studies
Rosa G. Castanon: The Salk Institute for Biological Studies
Joseph R. Nery: The Salk Institute for Biological Studies
Ah Young Lee: University of California, San Diego
Yuan Zhao: University of California, San Diego
Hui Huang: University of California, San Diego
Brian A. Williams: California Institute of Technology
Diane Trout: California Institute of Technology
Henry Amrhein: California Institute of Technology
Rongxin Fang: University of California, San Diego
Huaming Chen: The Salk Institute for Biological Studies
Bin Li: University of California, San Diego
Axel Visel: Lawrence Berkeley National Laboratory
Len A. Pennacchio: Lawrence Berkeley National Laboratory
Bing Ren: University of California, San Diego
Joseph R. Ecker: The Salk Institute for Biological Studies

Nature, 2020, vol. 583, issue 7818, 752-759

Abstract: Abstract Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited1,2. 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.

Date: 2020
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DOI: 10.1038/s41586-020-2119-x

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