title: DNA methylation at differentially methylated regions of imprinted genes is resistant to developmental programming by maternal nutrition.
abstract: The nutritional environment in which the mammalian fetus or infant develop is recognized as influencing the risk of chronic diseases, such as type 2 diabetes and hypertension, in a phenomenon that has become known as developmental programming. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, because epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. One class of genes that has been considered a potential target or mediator of programming events is imprinted genes, because these genes critically depend upon epigenetic modifications for correct expression and because many imprinted genes have roles in controlling fetal growth as well as neonatal and adult metabolism. In this study, we have used an established model of developmental programming-isocaloric protein restriction to female mice during gestation or lactation-to examine whether there are effects on expression and DNA methylation of imprinted genes in the offspring. We find that although expression of some imprinted genes in liver of offspring is robustly and sustainably changed, methylation of the differentially methylated regions (DMRs) that control their monoallelic expression remains largely unaltered. We conclude that deregulation of imprinting through a general effect on DMR methylation is unlikely to be a common factor in developmental programming.
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Chen
authors.forename: Anne
authors.initials: A
authors.lastname: Segonds-Pichon
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
authors.forename: Gavin
authors.initials: G
authors.lastname: Kelsey
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000235:genetics*; D018753:Diet, Protein-Restricted; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting / Q000235:genetics / Q000502:physiology; D039382:Maternal Nutritional Physiological Phenomena / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy