Alterations in gene expression presented here, combined with studies demonstrating alcohol's effects on methyl donors (Haycock, 2009), suggest that alcohol may impact transcriptional regulation, particularly DNA methylation. A recent study using 88 mM alcohol on cultured neural stem cells revealed that alcohol inhibits the methylation of Sox genes possibly resulting in upregulation of this transcription factor (Zhou et al., 2011); this is similar to increased mRNA expression of Sox3 after PAE presented here. Indeed, PAE also decreased mRNA levels of DNA methyltransferase 1 (Dnmt1) and 3a (Dnmt3a) in the proliferating culture of NPCs (Fig. 3A). DNMT1, known as the maintenance methyltransferase, is important for proper gene expression during neurogenesis (Ma et al., 2010), while DNMT3a is required for de novo methylation and is primarily localized to neural precursor cells during development (Feng, Chang, Li, & Fan, 2005). Conditional knockout of Dnmt1 and Dnmt3a results in hypomethylation of neuronal DNA resulting in loss of synaptic function (Feng et al., 2010). While we did observe an increase in Sox3 and Ndn expression (an imprinted gene requiring hypermethylation on one allele), other epigenetic
