Environmental stress experienced during early development can affect adult phenotypes through stable changes in gene expression. In C. elegans, stress experienced during the first larval stage, including starvation, crowding, and high temperature, promotes entry into the non-aging, stress-resistant dauer stage. Larva will exit dauer and resume continuous development when conditions improve. We have shown previously that postdauer (PD) adults retain a cellular memory of their developmental history that is reflected in changes of gene expression and behavior compared to continuously developing adults (CON). Recently, we have shown that the
osm-9 TRPV channel gene is down-regulated in ADL neurons of PD adults, while remains expressed in CON adults, resulting in altered olfactory behavior in response to high concentration of ascr#3 pheromone component. We identified a cis-acting promoter element called the PD motif that is required for the down-regulation of
osm-9 in PD ADL neurons, which is composed of a DAF-3 SMAD binding site adjacent to a 29 bp conserved sequence region. The PD motif is present in the upstream regulatory regions of 977 C. elegans genes and is bound by DAF-3 and ZFP-1 in PD animals. However, our mutational analysis of the PD motif indicates that additional transcription factors bind to the PD motif to both positively and negatively regulate
osm-9 expression. We have used a yeast one-hybrid approach performed by undergraduates in the laboratory and classroom to determine what other transcription factors are binding to the sequence components of the PD motif to regulate gene expression based on developmental history. Our preliminary results suggest that additional SMAD proteins acting in the TFG- beta pathway, DAF-8 and SMA-4, are also directly interacting with the PD motif. We are currently verifying and characterizing the role of transcription factors identified in our screen in the regulation of
osm-9 in C. elegans animals. Given that the PD motif is present in numerous genes, our results will contribute to the understanding of their regulation due to a TGF- beta sensitive PD motif.