Histone 3 modifications often associated with increased gene transcription have been noted in in vitro models and in the fetal cortex following gestational day 7 alcohol administration (Veazey et al., 2015). While not all epigenetics modifications were correlated with gene expression, upregulation of mRNA for the genes Tet1 (involved in hydroxymethylation) and the cell proliferation marker Ki67 were observed. Conversely, PAE from gestational days 7 – 21 reduced histone marks associated with activation and increased those associated with transcriptional repression in the hypothalamus in adulthood (Bekdash et al., 2013). The length of alcohol exposure, age, and brain region-specific differences in responsiveness to alcohol likely contribute to the opposing findings in these studies. Third trimester-equivalent alcohol exposure altered levels of CREB binding protein, a histone acetyltransferase, and acetylation of Histones 3 and 4 in the developing brain (Guo et al., 2011; Subbanna et al., 2014). P7 alcohol exposure also induced histone methylation and demonstrated that alcohol-induced apoptosis could be reduced through inhibition of the lysine dimethyltransferase G9a (Subbanna et al., 2013). These studies directly link histone modifications to neurodegenerative processes that could contribute to fetal alcohol effects (Figure 1).
