found that phospho-CREB was bound significantly to the promoters of 1743 genes, approximately 38% more genes than were occupied in saline-treated mice (1259) (Fig. 2A; Supplemental Tables S9 and S10). Roughly 12% of the phospho-CREB-bound genes after chronic cocaine exhibited cocaine-induced increases in histone acetylation, a marker of gene activation (Fig. 2A; Supplemental Table S11), suggesting that these genes are targets where phospho-CREB promotes transcription 24 hrs after chronic cocaine exposure. Interestingly, 10% of genes to which phospho-CREB is bound exhibit coincident increases in H3 dimethyl-K9/K27, a marker of repression, which suggests that phospho-CREB acts as a transcriptional repressor at certain genes (Mayr and Montminy, 2001). The overlapping gene lists of significant phospho-CREB binding and cocaine-induced changes in histone acetylation or methylation may represent the most likely targets where phospho-CREB alters gene activity 24 hrs after the last dose of cocaine.
