DNA methylation in mice is influenced by genetics as well as sex and life experience

Sara A. Grimm, Takashi Shimbo, Motoki Takaku, James W. Thomas, Scott Auerbach, Brian D. Bennett, John R. Bucher, Adam B. Burkholder, Frank Day, Ying Du, Christopher G. Duncan, John E. French, Julie F. Foley, Jianying Li, B. Alex Merrick, Raymond R. Tice, Tianyuan Wang, Xiaojiang Xu, Pierre R. Bushel, David C. Fargo, James C. Mullikin and Paul A. Wade ()
Additional contact information
Sara A. Grimm: Division of Intramural Research, NIEHS
Takashi Shimbo: Division of Intramural Research, NIEHS
Motoki Takaku: Division of Intramural Research, NIEHS
James W. Thomas: National Human Genome Research Institute
Scott Auerbach: National Toxicology Program, NIEHS
Brian D. Bennett: Division of Intramural Research, NIEHS
John R. Bucher: National Toxicology Program, NIEHS
Adam B. Burkholder: Division of Intramural Research, NIEHS
Frank Day: Division of Intramural Research, NIEHS
Ying Du: Division of Intramural Research, NIEHS
Christopher G. Duncan: Division of Intramural Research, NIEHS
John E. French: National Toxicology Program, NIEHS
Julie F. Foley: National Toxicology Program, NIEHS
Jianying Li: Division of Intramural Research, NIEHS
B. Alex Merrick: National Toxicology Program, NIEHS
Raymond R. Tice: National Toxicology Program, NIEHS
Tianyuan Wang: Division of Intramural Research, NIEHS
Xiaojiang Xu: Division of Intramural Research, NIEHS
Pierre R. Bushel: Division of Intramural Research, NIEHS
David C. Fargo: Division of Intramural Research, NIEHS
James C. Mullikin: National Human Genome Research Institute
Paul A. Wade: Division of Intramural Research, NIEHS

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract DNA methylation is an essential epigenetic process in mammals, intimately involved in gene regulation. Here we address the extent to which genetics, sex, and pregnancy influence genomic DNA methylation by intercrossing 2 inbred mouse strains, C57BL/6N and C3H/HeN, and analyzing DNA methylation in parents and offspring using whole-genome bisulfite sequencing. Differential methylation across genotype is detected at thousands of loci and is preserved on parental alleles in offspring. In comparison of autosomal DNA methylation patterns across sex, hundreds of differentially methylated regions are detected. Comparison of animals with different histories of pregnancy within our study reveals a CpG methylation pattern that is restricted to female animals that had borne offspring. Collectively, our results demonstrate the stability of CpG methylation across generations, clarify the interplay of epigenetics with genetics and sex, and suggest that CpG methylation may serve as an epigenetic record of life events in somatic tissues at loci whose expression is linked to the relevant biology.

Date: 2019
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DOI: 10.1038/s41467-018-08067-z

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