Alcohol could control cell cycle progression and, thus, contribute to delayed embryonic maturation through disruption of highly regulated developmental methylation patterns that are critical for the precise spatial and temporal expression of developmentally regulated genes. Zhou and colleagues (2011) found that alcohol delayed the DNA methylation program in cultured embryonic cells. Regions that showed the most disruption of DNMT1 activity also displayed significant growth reductions. DNMT1 is responsible for maintaining patterns of methylation and ensuring transmission of methylation marks during replication, making DNMT1 activity critical for cell memory and, potentially, multigenerational effects. Dysregulation of DNMT1, MeCP2, or one-carbon metabolism (Bekdash et al., 2013; Nagre et al., 2015; Ngai et al., 2015) represents one way that developmental alcohol exposure might influence methylation patterns across the lifespan, causing long-term changes to downstream gene expression and, ultimately, behavioral and cognitive impairments. Bekdash et al. (2013) reported long-term increases in expression of DNMT1 and MeCP2 in the hypothalamus of PAE adult rats. Another study reported decreased MeCP2 expression in the prefrontal cortex and striatum of rodents, which correlated with behavioral abnormalities associated with cortical
