The genome-wide acetylation patterns of H3 and H4 show interesting features similar to previous reports in cell culture (Li et al., 2007) (Supplemental Fig. S1). Levels of acetylated H3 and H4 were maximal between −500 to +200 bp, with acetylated H3 forming a bimodal peak and acetylated H4 forming a single peak over transcription start sites. Notably, these overall patterns were not significantly altered by chronic cocaine administration, indicating that, on average, cocaine increases the amount of acetylation on specific promoters (Fig. 1A) rather than altering the spatial distribution of acetylation within promoters (Supplemental Fig. S1). Representative examples of cocaine-regulated gene promoters illustrate both prototypical and less common patterns of H3 and H4 acetylation (Fig. 1B). The gene encoding CART (cocaine- and amphetamine-regulated transcript) showed significant hyperacetylation of both H3 and H4 at an overlapping region of its promoter, each of which was very similar to the genome-wide average shown in Supplemental Fig. S1. Two other genes that are upregulated by cocaine (Fosnaugh et al., 1995; Sivam, 1989) and display acetylation patterns similar to the genome-wide average are Arc (activity
