An additional outstanding question in the field concerns the mechanisms underlying the establishment and transmission of epigenetic marks across generations. Although it has been demonstrated that the reprogramming of DNA methylation occurs genome wide during ontogeny, some select loci including imprinted genes and classes of repeat/transposable elements are known to escape this process in part, suggesting that transgenerational epigenetic inheritance could be localized to these regions of the genome (Hackett et al, 2013; Lane et al, 2003). However, few epigenome-wide data sets of DMRs associated with models of cross-generational epigenetic inheritance have been generated and interrogated in the context of this idea. Interestingly, the cadherin gene Cdh15, containing a DMR exhibiting the second largest methylation difference in our data set, is a candidate imprinted gene in mice (Proudhon et al, 2012), as are two DMR-associated genes in the Dlg4 network exhibiting differential expression between THC and VEH groups (Begain and Dlgap2). Epigenetic changes of Dlgap2 (Chertkow-Deutsher et al, 2010) and Begain (Nagy et al, 2015) have already been implicated in neuropsychiatric phenotypes. However, a comparison of our gene set with
