Structure and properties of transcriptional networks driving selenite stress response in yeasts
- Equal contributors
1 Laboratoire de génétique moléculaire, ENS/CNRS UMR 8541 46 rue d'Ulm, 75005 Paris, France
2 Plate-forme transcriptome, IFR 36, 46 rue d'Ulm, 75005 Paris, France
3 Muséum national d'Histoire naturelle, 57 rue Cuvier 75005 PARIS, France
4 Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies de Saclay, 91191 Gif sur Yvette Cedex, France
5 Equipe de Bioinformatique Génomique et Moléculaire, INSERM UMR S726, Université Paris 7, 2 place Jussieu, 75251 Paris cedex 05, France
BMC Genomics 2008, 9:333 doi:10.1186/1471-2164-9-333Published: 15 July 2008
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 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.
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.