title: Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.
abstract: Early-life exposures are critical in fetal programming and may influence function and health in later life. Adequate maternal folate consumption during pregnancy is essential for healthy fetal development and long-term offspring health. The mechanisms underlying fetal programming are poorly understood, but are likely to involve gene regulation. Epigenetic marks, including DNA methylation, regulate gene expression and are modifiable by folate supply. We observed transcriptional changes in fetal liver in response to maternal folate depletion and hypothesized that these changes are concomitant with altered gene promoter methylation.
  
  
  
  Female C57BL/6J mice were fed diets containing 2 or 0.4 mg folic acid/kg for 4 wk before mating and throughout pregnancy. At 17.5-day gestation, genome-wide gene expression and promoter methylation were measured by microarray analysis in male fetal livers. While 989 genes were differentially expressed, 333 promoters had altered methylation (247 hypermethylated, 86 hypomethylated) in response to maternal folate depletion. Only 16 genes had both expression and methylation changes. However, most methylation changes occurred in genomic regions neighboring expression changes.
  
  
  
  In response to maternal folate depletion, altered expression at the mRNA level was not associated with altered promoter methylation of the same gene in fetal liver.
authors.affiliation: Human Nutrition Research Centre, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK. jill.mckay@ncl.ac.uk.
authors.forename: Jill A
authors.initials: JA
authors.lastname: McKay
authors.affiliation: Maastricht Centre for Systems Biology-MaCSBio, Maastricht University, Maastricht, the Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Adriaens
authors.affiliation: Department of Bioinformatics-BiGCaT, Maastricht University, Maastricht, the Netherlands.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Evelo
authors.affiliation: Human Nutrition Research Centre, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Dianne
authors.initials: D
authors.lastname: Ford
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
mesh_terms: D000818:Animals; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D005494:Folic Acid Deficiency / Q000196:embryology* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000187:drug effects / Q000196:embryology* / Q000502:physiology; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011401:Promoter Regions, Genetic
chemical_list: D005492:Folic Acid
keywords: DNA methylation; Development; Folate; Gene expression; Programming