ΔFosB displayed significant binding to a broad region of promoters genome-wide (−1500 to +250 bp) (Supplemental Fig. S1), similar to that of H3 dimethyl-K9/K27. As with histone acetylation and methylation, chronic cocaine did not significantly affect the average position of the genome-wide pattern of ΔFosB binding. ΔFosB was found to be strongly enriched on many genes previously implicated in behavioral responses to cocaine, as well as others that now warrant further investigation. Fig. 2B illustrates ΔFosB binding across the promoters of four representative genes after chronic cocaine. For each promoter, the figure shows where ΔFosB binding is enriched relative to the gene’s transcription start site and the location of the nearest consensus AP1 (activator protein 1) site (TGA[C/G]TCA) or near-consensus site (1 bp different). One ΔFosB target gene, Gpsm1 (AGS3, activator of G-protein signaling 3) is upregulated for weeks after cocaine exposure in the NAc and has been shown to be critically involved in behavioral responses to cocaine (Bowers et al., 2004). The stability and persistence of ΔFosB during weeks of drug withdrawal further support its role as a key
