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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.

Lookup NU author(s): Dr Jill McKay, Professor Dianne Ford, Professor John Mathers



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Scope; 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 hypothesised that these changes are concomitant with altered gene promoter methylation. Methods and Results; Female C57BL/6J mice were fed diets containing 2 mg or 0.4 mg folic acid/kg for 4 weeks 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. Whilst 989 geneswere 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 neighbouring expression changes. Conclusion; 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.

Publication metadata

Author(s): McKay JA, Adriaens M, Evelo CT, Ford D, Mathers JC

Publication type: Article

Publication status: Published

Journal: Molecular Nutrition and Food Research

Year: 2016

Volume: 60

Issue: 9

Pages: 2031–2042

Print publication date: 01/09/2016

Online publication date: 06/06/2016

Acceptance date: 04/04/2016

Date deposited: 18/07/2016

ISSN (print): 1613-4125

ISSN (electronic): 1613-4133

Publisher: Wiley


DOI: 10.1002/mnfr.201600079


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Funder referenceFunder name
North of England Children's Cancer Research (NECCR)
CT-2004-505944NuGO ("The European Nutrigenomics Organisation; linking genomics, nutrition and health research")