To determine how ΔFosB binding affects the expression of its target genes in the NAc after chronic cocaine exposure, we identified which ΔFosB gene targets also showed significant cocaine-induced changes in chromatin markers of gene activation or repression (see Supplemental Table S8). Roughly 13% of the significant ΔFosB gene targets in cocaine-treated mice exhibited coincident increases in histone acetylation, which suggests that ΔFosB may be acting as a transcriptional activator at these genes (Fig. 2A, Supplemental Table S8). ΔFosB is also known to act as a transcriptional repressor at certain genes, and while very few ΔFosB-bound genes showed hypoacetylation 24 hrs after chronic cocaine (Supplemental Fig. S2), roughly 8% of ΔFosB targets showed increased histone H3K9/27 methylation (Fig. 2A). These genes may represent targets where ΔFosB acts as a repressor. While statistical analysis did not reveal a significant interaction between ΔFosB binding and histone acetylation or methylation on a global scale, the overlapping gene lists may represent the specific targets where ΔFosB affects gene expression 24 hrs after the last dose of cocaine. Since we only analyzed ΔFosB binding 24
