Intriguingly, our previous genome-wide study exploring epigenetic alterations (DNA methylation) in the striatum of F1 offspring with parental germline THC exposure identified Dlg4 as the most significant hub within a functional network (Watson et al., 2015). The genes identified in that network, including several glutamate receptor subunits and other molecules involved in the regulation of synaptic plasticity (e.g. Grin2A and Dlgap3), contained differentially methylated regions on the DNA level, emphasizing the long-term epigenetic disruptions in gene regulation due to parental THC exposure. Interestingly, the dynamic control of glutamate receptors (e.g. receptor trafficking) has been demonstrated to be regulated by DNA methylation (Sweatt, 2016).
