The MSN2 and MSN4 genes encode homologous and functionally redundant Cys2His2 zinc finger proteins. A disruption of both MSN2 and MSN4 genes results in a higher sensitivity to different stresses, including carbon source starvation, heat shock and severe osmotic and oxidative stresses. We show that MSN2 and MSN4 are required for activation of several yeast genes such as CTT1, DDR2 and HSP12, whose induction is mediated through stress‐response elements (STREs). Msn2p and Msn4p are important factors for the stress‐induced activation of STRE dependent promoters and bind specifically to STRE‐containing oligonucleotides. Our results suggest that MSN2 and MSN4 encode a DNA‐binding component of the stress responsive system and it is likely that they act as positive transcription factors.

In all living organisms, appropriate reactions to unfavorable environmental conditions (stress factors) are observed. When transcription in eukaryotic cells is controlled by extracellular signals, at least one signaling component has to be translocated from the cytoplasm to the nucleus in a signal-dependent manner. The signaling components may be of low molecular weight (second messengers) or protein members of the signaling cascades. Examples for the latter are MAP kinases, for example, the p42 MAP kinase and p44 ERK1 on mitogenic stimulation (Chen et al. 1992).Regulated nuclear translocation is also found widely at the level of transcription factors and is achieved by either cytoplasmic anchoring or activation of nuclear localization signals (NLS) by unmasking or modification (Jans 1995;Gö rlich and Mattaj 1996;Nigg 1997). A prominent example of this type of control is provided by NF-B. A rapid transcriptional response to a variety of stress stimuli is elicited by phosphorylation of the inhibitory factor IB followed by its dissociation from the transcription factor and destruction. This leads to unmasking of the NF-B nuclear localization signal and to the subsequent translocation to the nucleus (Siebenlist, et al. 1995;Baldwin 1996). Another example is NF-ATc, a transcription factor involved in early immune responses that is translocated to the nucleus on dephosphorylation by Ca 2+

The HOG signal pathway of the yeast Saccharomyces cerevisiae is defined by the PBS2 and HOG1 genes encoding members of the MAP kinase kinase and of the MAP kinase family, respectively. Mutations in this pathway (deletions of PBS2 or HOG1, or point mutations in HOG1) almost completely abolish the induction of transcription by osmotic stress that is mediated by stress response elements (STREs). We have demonstrated previously that STREs also mediate induction of transcription by heat shock, nitrogen starvation and oxidative stress. This study shows that they are also activated by low external pH, sorbate, benzoate or ethanol stress. Induction by these other stress signals appears to be HOG pathway independent. HOG1‐dependent osmotic induction of transcription of the CTT1 gene encoding the cytosolic catalase T occurs in the presence of a protein synthesis inhibitor and can be detected rapidly after an increase of tyrosine phosphorylation of Hog1p triggered by high osmolarity. Consistent with a role of STREs in the induction of stress resistance, a number of other stress protein genes (e.g. HSP104) are regulated like CTT1. Furthermore, catalase T was shown to be important for viability under severe osmotic stress, and heat shock was demonstrated to provide cross‐protection against osmotic stress.

Transcription of the Saccharomyces cerevisiae ClTI gene encoding the cytosolic catalase T is activated by a variety of stress conditions: it is derepressed by nitrogen starvation and induced by heat shock. Furthermore, it is activated by osmotic and oxidative stress. This study shows that a CTT1 upstream region previously found to be involved in nitrogen, cAMP and heat control (base pairs -382 to -325) contains a UAS element (STRE, -368 to -356), which is sufficient for the activation of a reporter gene by all types of stress acting on CT1. Gel retardation experiments demonstrated the existence of a factor specifically binding to STRE, but to a lesser extent to mutated elements having partly or entirely lost the ability to mediate stress control. Heat activation of STRE, but not of a canonical heat shock element, is enhanced by a ras2 defect mutation, which enhances thermotolerance, and is dramatically reduced by a bcyl disruption mutation, which decreases thermotolerance. It can be hypothesized, therefore, that the novel stress control element is important for the establishment of induced stress tolerance.