International Summer School
	From Genome to Life:     Structural, Functional and Evolutionary approaches
	BOLOTIN FUKUHARA Monique  Institut de Génétique et Microbiologie -, Université Paris Sud -, 91405 Orsay, France title: Regulatory networks in the yeast S.cerevisiae : control of oxygen and carbon metabolism M. Pinto, H. Dumond, S. Buschlen, M. Bolotin-Fukuhara Institut de Génétique et Microbiologie (UMR 8621). Université Paris-Sud. 91405 Orsay Cedex   Several key transactivators are involved in the global transcriptional regulation of gene expression in S.cerevisiae in response to oxygen tension and carbon sources. Using different methods ( fusion libraries, macroarrays and transcriptome data obtained by Affymetrix chips), we have studied the role of two of them, YAP1 (the yeast protein similar to c-jun) necessary for the cell response to oxydative stress and the HAP complex involved in the fermentation-respiration shift (diauxic shift). Our results confirm the described function of these two transactivators and extend the number of genes regulated by them. YAP1 controls the expression of genes which are scavengers of ROS (reactive oxygen species) and which are necessary to balance the level of the reducing equivalents as could be expected for protection against oxydative stress. HAP4 induces the expression of genes involved in the Krebs cycle and the mitochondrial function when fermentative carbon sources are limiting or absent. However, a much more complex view of this global regulation has been revealed from a detailed analysis of the data obtained in different physiological conditions. We showed that YAP1 is also required in normoxic conditions and has an essential role in the control of cell proliferation, as its human homolog c-jun. We also identified genes which are negatively regulated by HAP4 ( such as genes involved in lipid biosynthesis), exemplifying the fine tuning role of the HAP complex in this important metabolic shift via the coordination of different metabolic pathways. These studies point out to two key points which have to be considered in approaching global gene expression analysis : the great interest to combine different global approaches to study expression net works and the particular attention in the choice of the physiological conditions to try to define a complex role for a key regulator. These points will be discussed as well the opening of these results for prospective functional evolution.