a sustained dietary change increases epigenetic variation in isogenic mice持续的饮食变化增加表观遗传变化同基因的老鼠.pdfVIP

A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice 1,2. 1,2. 3,4 1,2,5 6 Cheryl C. Y. Li , Jennifer E. Cropley , Mark J. Cowley , Thomas Preiss , David I. K. Martin , Catherine M. Suter1,2* 1Victor Chang Cardiac Research Institute, University of New South Wales, Sydney, Australia, 2 Faculty of Medicine, University of New South Wales, Sydney, Australia, 3 Peter Wills Bioinformatics Centre, Garvan Institute of Medical Research, Sydney, Australia, 4 Cancer Research Program, Garvan Institute of Medical Research, Sydney, Australia, 5 Faculty of Science, University of New South Wales, Sydney, Australia, 6 Children’s Hospital Oakland Research Institute, Oakland, California, United States of America 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, suggesti