Figure 2. Effect of maternal dietary supplementation on the phenotype and epigenotype of A^vy/a offspring.

a | Dietary supplementation of female mice during pregnancy. The diets of female a/a mice are supplemented with methyl-donating substances (that is, folic acid, choline, vitamin B₁₂ and betaine)¹⁹ or the phytoestrogen genistein²⁰ 2 weeks before mating with male A^vy/a agouti mice, and throughout pregnancy and lactation. b | Maternal dietary supplementation and coat-colour distribution in A^vy/a offspring. The coat colour is primarily yellow in the offspring that are born to unsupplemented mothers, whereas it is mainly brown in the offspring from mothers that were supplemented with methyl-donating compounds or genistein. Approximately 50% of the offspring from these matings are black (a/a) but, as they do not contain an A^vy allele, they are not shown here. c | DNA methylation and agouti gene expression. Maternal hypermethylating dietary supplementation shifts the average coat-colour distribution of the offspring to brown by causing an IAP (intracisternal A particle, shown as a green bar) upstream of the agouti gene to be more methylated on average than in offspring that are born to mothers fed an unsupplemented diet. Arrow size is directly proportional to the amount of ectopic and developmental agouti gene expression. White-filled circles indicate unmethylated CpG sites and black-filled circles indicate methylated CpG sites.