Another commonality between the consequences of early-life stress and alcohol are the observed alterations in levels of epigenetic regulators throughout the brain. For example, DNMT1 was found to be increased across the brain in animals with a history of early-life stress or alcohol exposure (Bekdash et al., 2013; Blaze and Roth, 2013; Dong et al., 2015; Pena et al., 2012). MeCP2, which is important for neurodevelopment, is another epigenetic regulator found to change after exposure to either stress or alcohol. Importantly, alcohol and stress studies have consistently found a reduction in MeCP2 expression in the frontal cortex (Blaze and Roth, 2013; Kim et al., 2013); reduced MeCp2 in the frontal cortex has been linked with developmental disorders (Gonzales and LaSalle, 2010; Nagarajan et al., 2006). These changes to epigenetic regulators could underlie the genome-wide and gene specific alterations observed in DNA methylation and posttranslational histone modifications. There is also evidence that changes to the epigenome resulting from developmental perturbations are potentiated by exposure to further insult (a “second-hit”) later in life (Hellemans et al., 2010; Park et al., 2017; Seo
