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.