Abstract
Epigenetic changes can be induced by adverse environmental exposures, such as nutritional imbalance, but little is known about the nature or extent of these changes. Here we have explored the epigenomic effects of a sustained nutritional change, excess dietary methyl donors, by assessing genomic CpG methylation patterns in isogenic mice exposed for one or six generations. We find stochastic variation in methylation levels at many loci; exposure to methyl donors increases the magnitude of this variation and the number of variable loci. Several gene ontology categories are significantly overrepresented in genes proximal to these methylation-variable loci, suggesting that certain pathways are susceptible to environmental influence on their epigenetic states. Long-term exposure to the diet (six generations) results in a larger number of loci exhibiting epigenetic variability, suggesting that some of the induced changes are heritable. This finding presents the possibility that epigenetic variation within populations can be induced by environmental change, providing a vehicle for disease predisposition and possibly a substrate for natural selection.
Highlights
Epigenetic modifications lie at the interface between genes and the environment, and have the potential to create functional diversity in response to environmental cues
We have investigated the extent of epigenetic changes induced by methyl donors, by assessing cytosine methylation at CpG island promoters across the genome in mice exposed to methyl donors for one or six generations
Epigenetic changes to gene expression that do not involve changes to DNA sequence can be influenced by the environment and provide one candidate mechanism by which early nutrition can influence adult disease risk
Summary
Epigenetic modifications lie at the interface between genes and the environment, and have the potential to create functional diversity in response to environmental cues. Epigenetic changes have been observed after early exposure to a variety of insults including environmental toxins [1], variations in maternal care [2], in vitro culture [3] and nutritional stressors [4,5,6,7,8,9,10,11,12]. The epigenetic response to altered nutrition is of great interest because it may explain how nutritional stress during gestation can have health effects beyond the neonatal period. Suboptimal nutrition or exposure to environmental toxins or stress during gestation increases the susceptibility of offspring to a number of adult-onset diseases, a phenomenon known as fetal programming [13]. It has been widely speculated that epigenetic changes underlie the phenotypic response to early nutritional stress [14,15,16,17], but the genes responsible for the phenotypic changes are not known, and few studies have examined the magnitude and extent of epigenetic changes in response to altered nutrition
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