ARS | Publication request: Maternal methyl supplements increase offspring DNA methylation at Axin Fused

Submitted to: Genesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 27, 2006
Publication Date: July 25, 2006
Citation: Waterland, R.A., Dolinoy, D.C., Lin, J.R., Smith, C.A., Shi, X., Tahiliani, K.G. 2006. Maternal methyl supplements increase offspring DNA methylation at axin fused. Genesis. 44(9):401-406.

Interpretive Summary: Previous studies show that maternal nutrition before and during pregnancy can affect gene expression and metabolism. We tested whether dietary supplementation before and during pregnancy affects gene expression of mouse offspring. We show that, similar to previously studied agouti viable yellow mice, DNA methylation in axin fused mice is affected by maternal diet. Unlike agouti viable yellow mice, however, the effect occurred specifically in tail. Our results indicate that DNA methylation at variable gene sites is, in general, characteristic of the response to maternal diet, and motivate the study of diet on gene expression in the human genome.

Technical Abstract: Transient environmental exposures during mammalian development can permanently alter gene expression and metabolism by influencing the establishment of epigenetic gene regulatory mechanisms. The genomic characteristics that confer such epigenetic plasticity upon specific loci, however, have not been characterized. Methyl donor supplementation of female mice before and during pregnancy permanently increases DNA methylation at the viable yellow agouti (Avy) metastable epiallele in the offspring. The current study tested whether another murine metastable epiallele, axin fused (AxinFu), similarly exhibits epigenetic plasticity to maternal diet. We found that methyl donor supplementation of female mice before and during pregnancy increased DNA methylation at AxinFu and thereby reduced by half the incidence of tail kinking in AxinFu/+ offspring. The hypermethylation was tail-specific, suggesting a mid-gestation effect. Our results indicate that stochastic establishment of epigenotype at metastable epialleles is, in general, labile to methyl donor nutrition, and such influences are not limited to early embryonic development.