A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice

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.

Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm

“…Unlike genetic polymorphisms such as SNPs and copy number variation, epigenetic polymorphisms can be influenced by both genetic and environmental determinants (Anway et al 2005;Li et al 2011;Crews et al 2012;Skinner et al 2012). In our study, we obtained biological replicates from two individuals for the breast, fetal brain, and blood data sets.…”

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…In animals, it has been demonstrated that long-term exposure to a methyl donor rich diet for six generations results in a large number of loci exhibiting epigenetic variability, suggesting that some of the induced changes are heritable (Li CC et al, 2011). The offspring of HFD-fed mice are more susceptible to develop hepatic steatosis when weaned on the same HFD than on normal chow .…”

Folate and Prevention of Neural Tube Disease

“…Therefore several reports support the hypothesis that folic acid likely acts through diverse mechanisms to influence neural tube closure (Li et al, 2011;Marean et al, 2011) so in future it will be of interest to determine the mechanistic basis of the specific gene-environment interactions that together influence neural tube closure.…”

“…Moreover folic acid also induces epigenetic changes during development and can conceivably affect the epigenetic regulation of gene expression (Lillycrop et al, 2005;Mathers et al, 2010;Li et al, 2011). Thus, the identification of genetic risk factors for human NTDs is complicated by the multiplicity of genes participating in neurulation, and the importance of gene-environment interactions (Greene et al, 2009a, b).…”