Links between social experiences and neural / endocrine responses have long been recognized, but the breadth of their impact on gene expression has only recently become apparent following the sequencing of the human genome. Early computational analyses of the human genome sequence suggested that promoter DNA sequences might provide for psychologically specific transcriptional responses. For example, any gene bearing the motif GGTACAATCTGTTCT in its promoter might potentially be stimulated by severe, overwhelming stress experiences that release cortisol, because the cortisol-stimulated glucocorticoid receptor (GR) binds specifically to that DNA motif. In contrast, genes bearing the CREB/ATF promoter motif TGACGTCA would be predicted to activate in response to active-coping, fight-or-flight stress responses associated with catecholamine release and beta-adrenergic receptor signaling. Based on the distribution of these promoter motifs across the human genome, it appears that these two distinct psychological stress experiences may trigger very different transcriptional responses. Genes predicted to be cortisol-responsive disproportionately encode receptors and other molecules involved in a cell’s “perception” of its local environment. In contrast, putative catecholamine-responsive genes include few receptors, but a high concentration of signal transduction
