DNA methylation signatures link prenatal famine exposure to growth and metabolism.

Nat Commun
Authors
Keywords
Abstract

Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics of prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on a genome-scale analysis of differential DNA methylation in whole blood after periconceptional exposure to famine during the Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by intermediate levels of DNA methylation and map to genes enriched for differential expression during early development. Validation and further exploratory analysis of six P-DMRs highlight the critical role of gestational timing. Interestingly, differential methylation of the P-DMRs extends along pathways related to growth and metabolism. P-DMRs located in INSR and CPT1A have enhancer activity in vitro and differential methylation is associated with birth weight and serum LDL cholesterol. Epigenetic modulation of pathways by prenatal malnutrition may promote an adverse metabolic phenotype in later life.

Year of Publication
2014
Journal
Nat Commun
Volume
5
Pages
5592
Date Published
2014 Nov 26
ISSN
2041-1723
URL
DOI
10.1038/ncomms6592
PubMed ID
25424739
PubMed Central ID
PMC4246417
Links
Grant list
R01 AG042190 / AG / NIA NIH HHS / United States
R01 HL067914 / HL / NHLBI NIH HHS / United States
R01-HL067914 / HL / NHLBI NIH HHS / United States
R01AG042190 / AG / NIA NIH HHS / United States