Transcriptional regulation of yeast peroxiredoxin gene TSA2 through Hap1p, Rox1p, and Hap2/3/5p

In Saccharomyces cerevisiae, the transcription of peroxiredoxin gene TSA2 is responsive to various reactive oxygen and nitrogen species. Redox-regulated transcriptional activators Yap1p, Skn7p, Msn2p/Msn4p have been shown to play a role in regulating TSA2 expression. In this study we show that the transcription of TSA2 is under complex control involving additional transcription factors Hap1p, Rox1p, and Hap2/3/5p. Deletion of HAP1 led to a 50% reduction of TSA2 transcriptional activity. As an intracellular oxygen sensor, heme stimulated TSA2 transcription by activating Hap1p. The induction of TSA2 by H2O2is also mediated in part through Hap1p. Countering the effects of Hap1p was a transcriptional repressor Rox1p. Deletion of ROX1 or mutation of Rox1p-binding site significantly activated TSA2 transcription. In addition, TSA2 activity was diminished in hap2Δ, hap3Δ, hap4Δ, and hap5Δ strains, but was stimulated upon overexpression of Hap4p. Hap2/3/5p may cooperate with Msn2/4p to activate TSA2 after diauxic shift. Finally, we demonstrated a role for kinases Ras1/2p and Hog1p in Msn2/4p-dependent activation of TSA2. In particular, Hog1p mediated the response of TSA2 to osmotic and oxidative stress. Taken together, our findings suggest that the expression of TSA2 is regulated by a group of transcription factors responsive differentially to stress conditions.