title: [Folates and fetal programming: role of epigenetics and epigenomics].
abstract: Folates are needed for synthesis of methionine, the precursor of S-adenosyl methionine (SAM). They play therefore a key role in nutrition and epigenomics by fluxing monocarbons towards synthesis or methylation of DNA and RNA, and methylation of gene transregulators, respectively. The deficiency produces intrauterine growth retardation and birth dejects. Folate deficiency deregulates epigenomic mechanisms related to fetal programming through decreased cellular availability of SAM. Epigenetic mechanisms of folate deficiency are illustrated by inheritance of coat colour of agouti mice model and altered expression of Igf2/H19 imprinting genes. Dietary exposure to fumonisin FB1 acts synergistically with folate deficiency on alterations of heterochromatin assembly. Deficiency in folate and vitamin B12 produces impaired fatty acid oxidation in liver and heart through imbalanced methylation and acetylation of PGC1-alpha and decreased expression of SIRT1, and long-lasting cognitive disabilities through impaired hippocampal cell proliferation, differentiation and plasticity and atrophy of hippocampal CA1. Deciphering these mechanisms will help understand the discordances between experimental models and population studies on folate supplementation.
authors.affiliation: Inserm U-954, Nutrition-Génétique-Exposition aux risques environnementaux, Faculté de Médecine, Université de Lorraine et Centre de Référence des Maladies Héréditaires du Métabolisme, CHU de Nancy. jean-louis.gueant@univ-lorraine.fr
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
authors.affiliation: Inserm U-954, Nutrition-Génétique-Exposition aux risques environnementaux, Faculté de Médecine, Université de Lorraine et Centre de Référence des Maladies Héréditaires du Métabolisme, CHU de Nancy.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Daval
authors.affiliation: L'Académie nationale de médecine.
authors.forename: Paul
authors.initials: P
authors.lastname: Vert
authors.affiliation: L'Académie nationale de médecine.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Nicolas
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic / Q000502:physiology*; D057890:Epigenomics; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D005494:Folic Acid Deficiency / Q000150:complications / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D051379:Mice; D009752:Nutritional Status / Q000235:genetics; D011247:Pregnancy
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
vernacular_title: Folates et programmation foetale: rôle des mécanismes nutrigénomiques et épigénomiques.