title: HIF-1 and SKN-1 coordinate the transcriptional response to hydrogen sulfide in Caenorhabditis elegans.
abstract: Hydrogen sulfide (H₂S) has dramatic physiological effects on animals that are associated with improved survival. C. elegans grown in H₂S are long-lived and thermotolerant. To identify mechanisms by which adaptation to H₂S effects physiological functions, we have measured transcriptional responses to H₂S exposure. Using microarray analysis we observe rapid changes in the abundance of specific mRNAs. The number and magnitude of transcriptional changes increased with the duration of H₂S exposure. Functional annotation suggests that genes associated with protein homeostasis are upregulated upon prolonged exposure to H₂S. Previous work has shown that the hypoxia-inducible transcription factor, HIF-1, is required for survival in H₂S. In fact, we show that hif-1 is required for most, if not all, early transcriptional changes in H₂S. Moreover, our data demonstrate that SKN-1, the C. elegans homologue of NRF2, also contributes to H₂S-dependent changes in transcription. We show that these results are functionally important, as skn-1 is essential to survive exposure to H₂S. Our results suggest a model in which HIF-1 and SKN-1 coordinate a broad transcriptional response to H₂S that culminates in a global reorganization of protein homeostasis networks.
authors: Department of Biochemistry, University of Washington School of Medicine, Seattle, Washington, United States of America. dlm16@uw.edu
authors: Dana L
authors: DL
authors: Miller
authors: Mark W
authors: MW
authors: Budde
authors: Mark B
authors: MB
authors: Roth
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D058977:Molecular Sequence Annotation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C541178:HIF-1 protein, C elegans; D012333:RNA, Messenger; D014157:Transcription Factors; C073702:skn-1 protein, C elegans; D006862:Hydrogen Sulfide