ChIP-chip analysis of histone acetylation in the NAc of cocaine-treated mice has provided new insight into both basic transcriptional mechanisms occurring in vivo as well as novel pathways involved in cocaine action. One such insight directly follows from a previous report using qChIP to analyze histone acetylation on a few genes already known to be involved in cocaine responses. On the small number genes studied, a pattern emerged whereby genes which are induced by acute cocaine (e.g. c-fos, fosb) were also hyperacetylated at histone H4, while genes which are induced by chronic cocaine (e.g. cdk5, bdnf) were hyperacetylated at histone H3 [53]. Similar findings were observed in acute and chronic seizure models [68]. Moreover, a switch between H4 and H3 acetylation was observed on the promoter of fosb, an immediate early gene which is induced after both acute and chronic 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
