title: Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.
abstract: A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults.
authors.affiliation: The Blizard Institute, Barts, and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. m.holland@qmul.ac.uk v.rakyan@qmul.ac.uk.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Holland
authors.affiliation: The Blizard Institute, Barts, and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Lowe
authors.affiliation: Division of Diabetes and Nutritional Sciences, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Caton
authors.affiliation: The Blizard Institute, Barts, and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gemma
authors.affiliation: The Blizard Institute, Barts, and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Carbajosa
authors.affiliation: The Blizard Institute, Barts, and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Amy F
authors.initials: AF
authors.lastname: Danson
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, CB2 0QQ, UK.
authors.forename: Asha A M
authors.initials: AA
authors.lastname: Carpenter
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, CB2 0QQ, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Loche
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, CB2 0QQ, UK.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
authors.affiliation: The Blizard Institute, Barts, and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. m.holland@qmul.ac.uk v.rakyan@qmul.ac.uk.
authors.forename: Vardhman K
authors.initials: VK
authors.lastname: Rakyan
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004275:DNA, Ribosomal / Q000235:genetics*; D059305:Diet, High-Fat; D018753:Diet, Protein-Restricted; D044127:Epigenesis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D009752:Nutritional Status; D009765:Obesity / Q000235:genetics; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D014886:Weaning
chemical_list: D004275:DNA, Ribosomal