The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2
Program in Systems Biology; Program in Molecular Medicine; UMass Metabolic Network
Cellular and Molecular Physiology | Genetics | Systems Biology
Cellular damage caused by reactive oxygen species (ROS) is believed to be a major contributor to age-associated diseases. Previously, we characterized the C. elegans Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans brap-2 mutants display increased expression of SKN-1-dependent phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAP kinase C. elegans ortholog). An RNAi screen was conducted using a transcription factor library to identify genes required for increased expression of the SKN-1 target gst-4 in brap-2 mutants. We identified ELT-3, a member of the GATA transcription factor family, as a positive regulator of gst-4p::gfp expression. We found that ELT-3 interacts with SKN-1 to activate gst-4 transcription in vitro and that elt-3 is required for enhanced gst-4 expression in the brap-2(ok1492) mutant in vivo Furthermore, nematodes overexpressing SKN-1 required ELT-3 for lifespan extension. Taken together, these results suggest a model where BRAP-2 acts as negative regulator of SKN-1 through inhibition of p38 MAPK activity and that the GATA transcription factor ELT-3 is required along with SKN-1 for the phase II detoxification response in C. elegans.
DOI of Published Version
Genetics. 2017 Jun 9. pii: genetics.116.198788. doi: 10.1534/genetics.116.198788. [Epub ahead of print] Link to article on publisher's site
Hu, Queenie; D'Amora, Dayana R.; MacNeil, Lesley T.; Walhout, Albertha J. M.; and Kubiseski, Terrance J., "The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2" (2017). Program in Systems Biology Publications and Presentations. 109.