Objectives Periconceptual folate supplementation is recommended to reduce the risk of fetal neural tube defect and other congenital defects. Folate is a source of methyl donors, and experimental data on rodents suggest it could influence DNA methylation and alter gene expression. Previously the authors demonstrated a statistically significant inverse correlation (p=0.001) between cord blood global DNA methylation and plasma homocysteine, a recognised inverse indicator of methyl donor supply. The aim of this study was to determine if these observed changes in global methylation were also apparent in putative gene promoters.
Materials and methods Cord blood DNA from babies with different levels of global DNA methylation was used for Methylated DNA Immunoprecipitation. Microarray analysis of enriched methylated DNA was used to examine the methylation status of more than 28 000 gene associted CpG islands. For array identified methylated regions, results were validated by bisulphite sequencing.
Results The microarray data demonstrated that, increasing global DNA methylation is accompanied by elevated methylation in promoters/CpG islands of a number of genes. Bioinformatics analysis of array data showed that mean methylation of CpG islands and surrounding shores increased with the increase in level of Global methylation, however, this was higher in the CpG shores compared to the islands.
Conclusion This is the first study demonstrating effects of prenatal maternal dietary exposure to methyl groups on fetal gene specific DNA methylation. Changes in DNA methylation can potentially play significant role in fetal programming and may determine the risk of adult-onset diseases.
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