Evolutionarily conserved transcription factors drive the oxidative stress response in Drosophila

As organisms are constantly exposed to the damaging effects of oxidative stress through both environmental exposure and internal metabolic processes, they have evolved a variety of mechanisms to cope with this stress. One such mechanism is the highly conserved p38 MAPK (p38K) pathway, which is known to be post-translationally activated in response to oxidative stress, resulting in the activation of downstream antioxidant targets. However, little is known about the role of p38K transcriptional regulation in response to oxidative stress. Therefore, we analyzed the p38K gene family across the genus to identify conserved regulatory elements. We found that oxidative stress exposure results in increased p38K protein levels in multiple species and is associated with increased oxidative stress resistance. We also found that the genomic locus includes conserved AP-1 and lola-PT transcription factor consensus binding sites. Accordingly, over-expression of these transcription factors in is sufficient to induce transcription of and enhances resistance to oxidative stress. We further found that the presence of a putative lola-PT binding site in the locus of a given species is predictive of the species' survival in response to oxidative stress. Through our comparative genomics approach, we have identified biologically relevant putative transcription factor binding sites that regulate the expression of and are associated with resistance to oxidative stress. These findings reveal a novel mode of regulation for genes and suggest that transcription may play as important a role in p38K-mediated stress responses as post-translational modifications.