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A maternal effect regulates global DNA methylation patterns

Loos, R.; Carola, V.; Audero, E.; Brini, E.; Lo Iacono, L.; Moles, A.; Bertone, P.; Gross, C. T.

2020-08-15 genomics
10.1101/2020.08.15.252239 bioRxiv
Show abstract

Variation in DNA methylation between individuals has been shown to be influenced by both genetic and environmental factors. However, the relative impact of genetic and non-genetic factors on DNA methylation patterns across the mammalian genome has not been systematically studied. We performed whole-genome methylation analysis in two inbred mouse strains, revealing striking differences in the global distribution of DNA methylation. Although global methylation patterns were indistinguishable for most genomic features, a significant increase in the number of unmethylated CpG-island promoters and first exons was observed between strains. Experiments using F1 reciprocal hybrid strains demonstrated that the genotype of the mother dictated global DNA methylation patterns. Cross-fostering experiments ruled out a postnatal maternal effect on these differences and suggested that they were driven by a prenatal maternal effect, possibly via differential deposition of maternal gene products into the oocyte or uterine environment. These data demonstrate that maternal effects have a major impact on global DNA methylation patterns.

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