To gain insight into how phospho-CREB binding after chronic cocaine may alter gene activity, we compared our phospho-CREB ChIP-chip data to gene expression data from mice overexpressing CREB or its dominant negative, mCREB, in the NAc (McClung and Nestler, 2003). Importantly, inducible overexpression of mCREB in the NAc oppositely regulates most of the gene expression changes observed after CREB overexpression (Fig. 2C). The high degree of overlap between phospho-CREB binding and CREB-induced changes in gene expression provides further confidence in our phospho-CREB ChIP-chip data and suggests that most genes to which phospho-CREB is bound after chronic cocaine are indeed bona fide CREB targets.
