Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, Zhang Y, Slieker RC, Stok AP, Thijssen PE, Müller F, van Zwet EW, Bock C, Meissner A, Lumey LH, Eline Slagboom P, Heijmans BT. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun. 2014 Nov 26; 5:5592.

Citation

Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, Zhang Y, Slieker RC, Stok AP, Thijssen PE, Müller F, van Zwet EW, Bock C, Meissner A, Lumey LH, Eline Slagboom P, Heijmans BT. 2014. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nature communications. 5:5592. Pubmed: 25424739 DOI:10.1038/ncomms6592

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.

Related Faculty

Alexander Meissner, Ph.D.

The Meissner laboratory uses genomic tools to study stem cell biology with a particular focus on epigenetic reprogramming.