Genome-wide
analysis of the response to cell wall mutations in the yeast S. cerevisiae.
Arnaud Lagorce (1),
Nicole Hauser (2), Delphine Labourdette (1), Cristina Rodriguez (3), Hélène
Martin-Yken (1), Javier Arroyo (3), Jörg Hoheisel (2), Jean François (1)
(1) INSA / GBA, UMR-CNRS 5504 & INRA 792, 135 av de Rangueil, Toulouse
cedex 4, 31400, France (lagorce@insa-tlse.fr); (2) Division of Functional
Genome Analysis, DKFZ, 69120 Heidelberg, Germany; (3) Facultad de Farmacia,
Universidad Complutense de Madrid, 28040 Madrid, Spain
Perturbations of the yeast wall trigger a repair mechanism that reconfigures its molecular structure to preserve cell integrity. To investigate this mechanism, we compared the global gene expression using DNA-arrays in five cell wall mutants affected in a different manner in the cell wall architecture. Altogether, 300 responsive genes were kept and clustering methods isolated a single group of ~80 up-regulated genes that could be considered as the stereotypical transcriptional response of the cell wall compensatory mechanism. The in silico analysis of the DNA upstream region of these co-regulated genes revealed pair wise combinations of DNA-binding sites for transcriptional factors implicated in stress and heat shock responses (Msn2/4p and Hsf1p) with Rlm1p and Swi4p, two PKC1-regulated transcription factors involved in the activation of cell wall and G1 to S -regulated genes, respectively. Moreover, this computational analysis also uncovered the 6-bp 5'-AGCCTC-3' CDRE-motif in 40% of the co-regulated genes. This motif was recently shown to be the DNA binding site for Crz1p, the major effector of calcineurin-regulated gene expression. Taken altogether, our data lead to the conclusion that the cell wall compensatory mechanism integrates three major regulatory systems; namely the PKC1-SLT2 MAP kinase-signaling module, the 'global stress' response mediated by Msn2/4p and the Ca++/calcineurin dependent pathway.