Chunk #26 — Results — DMR-Associated Genes in the Dlg4 Network Exhibit Differential mRNA Expression in the NAc Adult F1 Offspring from THC-Exposed Lines
We had previously found expression of Grin2a to be associated with the cross-generational effects of THC exposure in the NAc of a cohort of F1 adult male rats (Szutorisz et al, 2014). In the present study, we identified a significant hypomethylated DMR located within the first coding exon of Grin2a (Figure 2c). Reanalysis of an expanded male/female cohort revealed significant downregulation of Grin2a mRNA levels (P=0.049; Table 3), consistent with our previous findings, and suggestive of a possible link between observed methylation differences and gene expression. To further explore potential effects of differential methylation on gene transcript levels, we conducted mRNA expression analysis for Dlg4 and eight additional DMR-associated genes in the Dlg4 protein–protein interaction network, as well as three genes overlapped by top DMRs presented in Table 1 (Table 3). In total, 5 out of 10 genes in the Dlg4 network (Dlgap2, Kcna5, Begain, Grin2a, and Dlg4) showed significant differential expression between THC and VEH groups (P<0.05; Table 3). Of the three genes associated with top DMRs that were tested, Mta1 tended to have higher expression in THC animals,