A sequenced human genome also provided new analytic infrastructure for mapping the molecular signaling pathways that convert socio-environmental conditions into differential gene expression. One approach reverses the normal flow of biological information from the environment, through transcription factor activity, and into gene expression (Figure 1). This analysis scans the promoters of differentially expressed genes to identify transcription factor-binding motifs that are over-represented in activated promoters, and thus reflect which specific transcription factors drove the observed differences in gene expression (Cole, Yan, Galic, Arevalo, & Zack, 2005). This approach has uncovered some surprising differences between the transcriptional signals “sent” by the brain, and the transcriptional signals “heard” by the human genome. In studies of chronic loneliness and threat of social loss (Cole et al., 2007; Miller et al., 2008), analyses indicated that the inflammation-driving NF-κB transcription factor played a key role in orchestrating both patterns of differential gene expression. Results also suggested that the GR was failing to inhibit NF-κB’s pro-inflammatory activity as it should. Neither study found decreases in circulating cortisol levels that might explain the reduced GR activity. If
