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


RESULTS
Selenite rapidly activates a battery of transcriptional circuits, including iron deprivation, oxidative stress and protein degradation responses. The mRNA levels of several transcriptional regulators are themselves regulated. We demonstrate the existence of a positive transcriptional loop connecting the regulator of proteasome expression, Rpn4p, to the pleiotropic drug response factor, Pdr1p. We also provide evidence for the involvement of this regulatory module in the oxidative stress response controlled by the Yap1p transcription factor and its conservation in the pathogenic yeast C. glabrata. In addition, we show that the drug resistance regulator gene YRR1 and the iron homeostasis regulator gene AFT2 are both directly regulated by Yap1p.


CONCLUSIONS
This work depicted a highly interconnected and complex transcriptional network involved in the adaptation of yeast genome expression to the presence of selenite in its chemical environment. It revealed the transcriptional regulation of PDR1 by Rpn4p, proposed a new role for the pleiotropic drug resistance network in stress response and demonstrated a direct regulatory connection between oxidative stress response and iron homeostasis.
Salin
Hélène
H
Laboratoire de génétique moléculaire, ENS/CNRS UMR 8541 46 rue d'Ulm, 75005 Paris, France. helene.salin@laposte.net
Fardeau
Vivienne
V
Piccini
Eugenia
E
Lelandais
Gaelle
G
Tanty
Véronique
V
Lemoine
Sophie
S
Jacq
Claude
C
Devaux
Frédéric
F
D041221:Candida glabrata / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D007501:Iron / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012331:RNA, Fungal / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D018038:Sodium Selenite / Q000633:toxicity*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
C436328:Aft2 protein, S cerevisiae; D004268:DNA-Binding Proteins; C085480:PDR1 protein, S cerevisiae; D012331:RNA, Fungal; C119430:RPN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; C481277:Yrr1 protein, S cerevisiae; D007501:Iron; D018038:Sodium Selenite