However, all investigations of cocaine-induced changes in gene expression to date have focused by necessity on measures of steady-state mRNA levels, which may not reflect the transcriptional regulation of the encoding genes. Recent advances in chromatin biology have made it possible for the first time to extend this level of knowledge to direct examination of transcriptional mechanisms. Thus, we now know, largely from studies of non-neural tissue, that the state of activation or repression of a gene is typically reflected in the covalent modifications of histone proteins in the gene’s vicinity (Kouzarides, 2007). The vast majority of reports indicate that increased acetylation of histone H3 or H4 is highly predictive of gene activation, while increased methylation of H3 at K9 or K27 (Lys9 or 27) is predictive of gene repression. Chromatin immunoprecipitation (ChIP), where tissue is lightly fixed to crosslink DNA with histones and other DNA-binding proteins and then immunoprecipitated for a protein of interest (e.g., acetylated H3), can be used to assess the extent to which a given gene is associated with these markers of activation or repression. For
