Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Author Riva Oliveira, Jess Abate, Kieran Dilks, Jessica Landis, Jasmine Ashraf, Coleen Murphy, Keith Blackwell Publication Year 2009 Type Journal Article Abstract Studies in model organisms have identified regulatory processes that profoundly influence aging, many of which modulate resistance against environmental or metabolic stresses. In Caenorhabditis elegans, the transcription regulator SKN-1 is important for oxidative stress resistance and acts in multiple longevity pathways. SKN-1 is the ortholog of mammalian Nrf proteins, which induce Phase 2 detoxification genes in response to stress. Phase 2 enzymes defend against oxygen radicals and conjugate electrophiles that are produced by Phase 1 detoxification enzymes, which metabolize lipophilic compounds. Here, we have used expression profiling to identify genes and processes that are regulated by SKN-1 under normal and stress-response conditions. Under nonstressed conditions SKN-1 upregulates numerous genes involved in detoxification, cellular repair, and other functions, and downregulates a set of genes that reduce stress resistance and lifespan. Many of these genes appear to be direct SKN-1 targets, based upon presence of predicted SKN-binding sites in their promoters. The metalloid sodium arsenite induces skn-1-dependent activation of certain detoxification gene groups, including some that were not SKN-1-upregulated under normal conditions. An organic peroxide also triggers induction of a discrete Phase 2 gene set, but additionally stimulates a broad SKN-1-independent response. We conclude that under normal conditions SKN-1 has a wide range of functions in detoxification and other processes, including modulating mechanisms that reduce lifespan. In response to stress, SKN-1 and other regulators tailor transcription programs to meet the challenge at hand. Our findings reveal striking complexity in SKN-1 functions and the regulation of systemic detoxification defenses. Keywords Animals, Down-Regulation, Gene Expression Regulation, Transcription, Genetic, Transcription Factors, RNA, Messenger, Oligonucleotide Array Sequence Analysis, DNA-Binding Proteins, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Longevity, Reactive Oxygen Species, Arsenites, DNA, Helminth, NF-E2-Related Factor 1, tert-Butylhydroperoxide Journal Aging Cell Volume 8 Issue 5 Pages 524-41 Date Published 09/2009 Alternate Journal Aging Cell Google ScholarBibTeXEndNote X3 XML