Altered fetal gene expression patterns after alcohol exposure have been reported,48–51 but the mechanism underlying alcohol-induced changes in gene expression remains to be elucidated. In the current study, we used an established whole-embryo culture system with strictly controlled staging (timed by somite number) and alcohol dose to investigate the effect of alcohol exposure during early embryo development on genome-wide DNA methylation patterns. Methyl-DNA immunoprecipitation followed by microarrays (MeDIP-chip) was used for DNA methylation mapping and measurement across the mouse embryo genome. The methylation microarray data was validated using Sequenom Mass ARRAY and correlated with gene expression data. Average methylation signals in the entire promoter region were used to characterize mouse embryo DNA methylation profiles. In addition, a novel two-consecutive probe analysis was employed to detect alcohol-induced methylation changes in localized genomic regions (the same direction change of two probes stretched over 150 nucleotides). Based on our integrated analysis, we conclude that alcohol exposure during early neurulation induces significant changes in DNA methylation patterns and gene expression that may contribute to FASD development.
