Assaying gene expression across the BXD panel allowed us to analyze how genetic variation influenced transcriptional responses to ethanol (Figure 2). As seen with other heritable complex traits measured in genetic mapping panels, the transcript-level response of most ethanol sensitive genes followed a continuous distribution across the BXD and progenitor strains. There was a subset of genes almost uniformly up-regulated by ethanol, including Npas4 (Figure 2b), Fos, Hsp8, Egr2, Dusp1 and Jun, all of which are neuronal activity dependent. Most genes, however, exhibited divergent ethanol responses between variable subsets of BXD strains (Figure 2a). While continuous distributions of transcriptional responses to ethanol were observed in all profiled regions, transcript-level changes were highly region specific. That is, we found little correspondence between a gene's ethanol response across regions. Even among the 399 genes found to be significantly ethanol responsive in all three brain regions, inter-region S-score correlations were effectively null (Figure S2). Therefore, acute ethanol effects on gene expression were modulated by both genetic background and brain regional environment factors.
