Li, Cheryl C. Y.Cropley, Jennifer E.Cowley, Mark J.Preiss, ThomasMartin, David I. K.Suter, Catherine M.2015-10-252015-10-251553-7404http://hdl.handle.net/1885/16064Epigenetic 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.This work was supported by the Australian Research Council (DP0771859) and the National Health and Medical Research Council (#459412, #635510).© 2011 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.5-methylcytosineallelesanimalscpg islandscytosinedna methylationdietary supplementsenvironmentgene expressiongenetic locimicemice, inbred c57blphenotypeprincipal component analysispromoter regions, geneticrepetitive sequences, nucleic acidstochastic processessulfitesepigenesis, geneticgenetic variation2011-04-2110.1371/journal.pgen.10013802015-12-09