Figure 2.

Changes in gene expression in cocaine versus food self-administering mice correlate with H3.3 deposition in promoters. A, H3.3-HA animals self-administered food for 10 consecutive days. Animals were implanted with catheters and given access to either food or cocaine for an additional 19 d following recovery from surgery. Twenty-four hours after the last operant session, NAcc tissue was collected. One side of the brain was processed for RNA-seq, and the other side was prepared for HA ChIP-seq. B, Transgenic HA-tagged male mice earned the same number of rewards (food or cocaine) both during the training phase, when all mice received food, and during the extended access to either food or cocaine. C, Principal component analysis of RNA-seq data revealed that principal component 2, which accounts for 16.9% of variability, is likely cocaine exposure. D, Distribution of annotated peaks resulting from the HA ChIP analysis revealed a preferential deposition of the tagged H3.3 protein near promoter and exon regions compared with a random distribution genomewide. E, Overexpression of 5 genes in cocaine-trained versus food-trained mice (Table 1) is confirmed by qPCR. *p < 0.05 versus food.