Fzf1p regulates an inducible response to nitrosative stress in Saccharomyces cerevisiae.
The mechanisms by which microorganisms sense and detoxify nitric oxide (*NO) are of particular interest due to the central role this molecule plays in innate immunity. We investigated the genetic basis of inducible nitric oxide (*NO) detoxification in Saccharomyces cerevisiae by characterizing the genome-wide transcriptional response to exogenously supplied *NO. Exposure to the *NO-generating compound dipropylenetriamine NONOate resulted in both a general stress response as well as a specific response characterized by the induction of a small set of genes, including the yeast flavohemoglobin YHB1, SSU1, and three additional uncharacterized open reading frames. Transcriptional induction of SSU1, which encodes a putative sulfite transporter, has previously been shown to require the zinc finger transcription factor Fzf1p. Deletion of Fzf1p eliminated the nitrosative stress-specific transcriptional response, whereas overexpression of Fzf1p recapitulated this response in the absence of exogenously supplied *NO. A cis-acting sequence unique to the promoter regions of Fzf1p-dependent genes was found to be sufficient to activate reporter gene activity in an *NO- and Fzf1p-dependent manner. Our results suggest that the presence of *NO or *NO derivatives activates Fzf1p leading to transcriptional induction of a discrete set of target genes that function to protect the cell from *NO-mediated stress.
Sarver
Aaron
A
Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA
DeRisi
Joseph
J
D000475:Alkenes / Q000494:pharmacology; D000595:Amino Acid Sequence; D027321:Anion Transport Proteins / Q000378:metabolism; D001483:Base Sequence; D017124:Conserved Sequence; D049308:Dioxygenases; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D006420:Hemeproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D000475:Alkenes; D027321:Anion Transport Proteins; C090870:FZF1 protein, S cerevisiae; D006420:Hemeproteins; D020030:Nitric Oxide Donors; D029701:Saccharomyces cerevisiae Proteins; C108311:Ssu1 protein, S cerevisiae; D014157:Transcription Factors; C453079:dipropylenetriamine-NONOate; D009569:Nitric Oxide; D049308:Dioxygenases; C101796:YHB1 protein, S cerevisiae