Abstract
BackgroundStress 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.ResultsSelenite 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.ConclusionThis 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.
Highlights
Stress responses provide valuable models for deciphering the transcriptional networks controlling the adaptation of the cell to its environment
No transcriptional regulation has been described for PDR1, but YAP1, RPN4 and PDR3 are induced by stress [3,5,6]
Gene ontology mapping of the selenite response We analyzed the transcriptome of S. cerevisiae cells treated with 1 mM sodium selenite for 2, 5, 10, 20, 40, 60 and 80 minutes
Summary
Stress responses provide valuable models for deciphering the transcriptional networks controlling the adaptation of the cell to its environment. At least eight different transcription factors act together to define the first-hour response of yeast cells to the toxic metalloid arsenite [3] These global and rapid responses are highly dynamic, involving sequential waves of gene activation and repression [1,2,4]. In these growth conditions, the expression of PDR1 and RPN4 was coordinated through a positive transcriptional loop This loop contributed to the optimal Yap1p-dependent oxidative stress induction of several genes encoding membrane proteins, including FLR1, ATR1 and FRM2. This function seemed to be conserved in the pathogenic yeast species C. glabrata. Our data provide evidence for direct transcriptional regulation of the iron homeostasis regulator Aft2p and of the multidrug resistance regulator Yrr1p by Yap1p, indicating a broader role for this factor in coordination of the oxidative stress response
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