cocaine [53]. Genome-wide ChIP-chip analysis reveals that while there are more H3 acetylated genes in the NAc of mice exposed to chronic cocaine, there is also a significant set of previously unrecognized, chronically-induced genes that are hyperacetylated only on H4 (Figure 2D) [67]. There was also an even smaller subset of genes which were acetylated on both histones H3 and H4. The mechanisms which determine whether a gene is hyperacetylated at H3 or H4 remain unclear, but these new data suggest that after chronic cocaine, there may be two distinct pathways to activate gene expression, one through acetylation of H3 and the other through H4. Additionally, these data also suggest that the H4 to H3 switch observed in both cocaine and seizure models may be reserved for certain types of genes, such as immediate early genes.
