Structure and properties of transcriptional networks driving selenite stress response in yeasts

Abstract

Background: Stress responses provide valuable models for deciphering the transcriptional networks controlling the adaptation of the cell to its environment. We analyzed the transcriptome response of yeast to toxic concentrations of selenite. We used gene network mapping tools to identify functional pathways and transcription factors involved in this response. We then used chromatin immunoprecipitation and knock-out experiments to investigate the role of some of these regulators and the regulatory connections between them.

Selenite-induced cell death in Saccharomyces cerevisiae: protective role of glutaredoxins

“…In this context, decreasing the ratio between GSH and oxidized glutathione after selenite-induced oxidative stress would influence cell viability. In addition, the latter transcriptomic study suggests that selenite also influences intracellular iron homeostasis by interfering with mitochondrial iron-sulphur cluster synthesis (Salin et al, 2008). The results of the present study demonstrating the importance of GSH-dependent Grx1p and Grx2p activity for protection against non-apoptotic death emphasize the role of GSH in defence against Se toxicity.…”

“…The importance of GSH-mediated protection against Se is confirmed by observations from two global analyses in S. cerevisiae: (i) the overrepresentation of mutants in GSHmediated pathways among those mutants displaying selenite hypersensitivity (Seitomer et al, 2008); and (ii) the transcriptional induction of genes involved in these same pathways upon selenite treatment (Salin et al, 2008). In this context, decreasing the ratio between GSH and oxidized glutathione after selenite-induced oxidative stress would influence cell viability.…”

“…Transcriptome analysis of selenite-treated S. cerevisiae cells reveals overlapping of the Se and oxidative stress responses, by the common upregulation of genes for oxidoreductases and for proteasome protein components (Salin et al, 2008). This suggests that Se also causes damage to proteins.…”

“…Accordingly, yeast mutants defective in the RAD9-mediated DNA repair pathway or the RAD6/RAD18-mediated DNA damage tolerance pathway are hypersensitive to sodium selenite (Seitomer et al, 2008), pointing to the importance of DNA damage in explaining Se toxicity to yeast cells. Analyses of mutants have also demonstrated the importance of the base excision repair pathway in tolerance to selenite (Mániková et al, 2010).Transcriptome analysis of selenite-treated S. cerevisiae cells reveals overlapping of the Se and oxidative stress responses, by the common upregulation of genes for oxidoreductases and for proteasome protein components (Salin et al, 2008). This suggests that Se also causes damage to proteins.…”

Yap4 PKA‐ and GSK3‐dependent phosphorylation affects its stability but not its nuclear localization

“…Yap4 belongs to this family and it has previously been shown that the gene encoding this protein is responsive to several forms of stress (Nevitt et al, 2004b;Salin et al, 2008). Its expression is regulated under osmotic stress by Hog1/Msn2 via two stress-response elements (STRE), and under oxidative stress by Msn2 and Yap1 through the STRE and Yap1 binding sites, respectively (Nevitt et al, 2004a).…”