Genetics, sex and life experience influence DNA methylation in the mouse

Methylation of DNA is an essential epigenetic mark in mammals, intimately involved in gene regulation. The extent to which genetics, sex, and life experience influence genomic DNA methylation patterns are matters of intense current interest. We addressed this issue by intercrossing inbred mouse strains and analyzing DNA methylation at the base-pair level across the genome in somatic tissue from parents and from age-matched offspring of multiple families. In comparison across genotype, tens of thousands of differentially methylated CpG residues and thousands of differentially methylated regions were detected. Differential methylation at these loci was preserved on parental alleles in offspring, suggesting that CpG methylation is a very stable epigenetic mark largely preserved across generation, correlating with DNA sequence. In comparison of autosomal DNA methylation patterns across sex, thousands of differentially methylated CpG residues and hundreds of differentially methylated regions were detected, consistent with known biological parameters that differ between males and females. Finally, comparison of individual groups of animals within our study revealed a CpG methylation pattern that likely results from pregnancy and/or lactation that was restricted to female animals who had borne offspring, signifying that CpG methylation may provide a record of major life events. Collectively, our results demonstrate the stability of CpG methylation across generation, clarify the interplay of epigenetics with genetics and sex, and suggest that CpG methylation may serve as an epigenetic record of life events. Methylation profiles of C57BL/6N mice, C3H/HeN mice, and their offspring were determined by whole-genome bisulfite sequencing.