[
International Worm Meeting,
2011]
All living organisms require a stable internal environment to develop, function and survive. This internal homeostasis is constantly challenged by a variety of potentially harmful stressors. In the attempt to reestablish homeostasis, many cellular processes are adjusted by modulating gene expression. Our laboratory has identified a largely uncharacterized and evolutionarily conserved stress-response pathway in C. elegans that regulates the expression of hundreds of genes following a variety of stress conditions. This network is named after the regulatory sequence that drives stress-induced gene expression; ESRE for ethanol and stress-response element. The ESRE stress-response network in C. elegans includes SLR-2, a C2H2 zinc finger protein, and its downstream target JMJC-1, a jumonji-C domain-containing protein that functions as a histone modifier. Recently we have identified an additional regulator of the ESRE-dependent transcription, C08B11.3/BAF200, which encodes for a conserved subunit of the PBAF chromatin-remodeling complex. Interestingly, the effect of C08B11.3 on the ESRE-gene expression appears to be tissue-specific; RNAi-mediated knockdown of C08B11.3 reduces ESRE-dependent transcription in ectoderm (neural and hypodermal tissue) but has no effect on endoderm expression. Currently, our primary goal is to identify the direct ESRE-binding protein (EBP). We are undertaking two complementary approaches - biochemical affinity purification using the oligonucleotide-trapping method and focused RNAi screening of candidate EPB factors in C. elegans. In vitro and in vivo studies will be used to further evaluate potential EBP candidates. Identifying the EBP, as well as additional ESRE-pathway regulatory components, will enable us to better understand the complex cellular networks that coordinate stress response.