title: 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.
authors.affiliation: Victor Chang Cardiac Research Institute, University of New South Wales, Sydney, Australia.
authors.forename: Cheryl C Y
authors.initials: CC
authors.lastname: Li
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cropley
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cowley
authors.forename: Thomas
authors.initials: T
authors.lastname: Preiss
authors.forename: David I K
authors.initials: DI
authors.lastname: Martin
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Suter
mesh_terms: D044503:5-Methylcytosine / Q000032:analysis*; D000483:Alleles; D000818:Animals; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation; D019587:Dietary Supplements / Q000009:adverse effects*; D004777:Environment; D044127:Epigenesis, Genetic; D015870:Gene Expression; D056426:Genetic Loci; D014644:Genetic Variation; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013269:Stochastic Processes; D013447:Sulfites / Q000032:analysis*
chemical_list: D013447:Sulfites; D044503:5-Methylcytosine; D003596:Cytosine; C042345:hydrogen sulfite