Numerous genes, shown in previous studies to be upregulated in NAc after chronic cocaine, were found in our ChIP-chip data to be associated with hyperacetylation of H3 or H4. Examples of such genes are listed in Table 1 (see Supplemental Tables S1-S3 for complete gene lists). Importantly, many of these individual genes have been directly related to aspects of neural and behavioral plasticity associated with cocaine exposure (see below). These observations provide important validation for our ChIP-chip approach and highlight the potential significance of the >1000 other genes that show similar markers of activation in this study. To experimentally determine the quality of our new ChIP-chip data sets, we performed quantitative ChIP on independent cohorts of saline and cocaine-treated mice. Analysis of 20 randomly selected target genes revealed that our ChIP-chip data have a false-positive rate of 25% – 15 out of 20 genes demonstrated statistically significant cocaine-induced changes in histone acetylation and 3 additional genes showed non-significant trends (see Supplemental Information). These findings demonstrate that our new gene lists are of excellent quality, especially given that they are derived from in vivo tissue samples of adult brain.
