Third, we interpret the responses of genes with known functions to gain insights into the physiological effects of each of the stresses as well as the mechanisms that yeast cells use to cope with these stresses. The roles of the transcription factor Yap1p and the related factors Msn2p and Msn4p are examined by analyzing the expression responses of strains deleted for or overproducing these factors. Second, several sets of coregulated genes share promoter elements, which point to the involvement of specific transcription factors in the regulation of those genes. First, we describe the global expression programs in response to a diverse set of stresses, including their specific features and a common response to all of the stressful conditions, termed the “environmental stress response” (ESR). Our analysis of this large body of gene expression data allowed us to define stereotyped patterns of gene expression during the adaptation to stressful environments, and to compare and contrast the gene expression responses to different stresses. We used DNA microarrays to analyze changes in transcript abundance in yeast cells responding to a panel of diverse environmental stresses.
Several regulatory systems have been implicated in modulating these responses, but the complete network of regulators of stress responses and the details of their actions, including the signals that activate them and the downstream targets they regulate, remain to be elucidated. Other gene expression responses appear to be specific to particular environmental conditions. Genes whose transcription is responsive to a variety of stresses have been implicated in a general yeast response to stress ( Mager and De Kruijff, 1995 Ruis and Schuller, 1995). The complexity of the yeast cell's system for detecting and responding to environmental variation is only beginning to emerge.
Thus, when environmental conditions change abruptly, the cell must rapidly adjust its genomic expression program to adapt to the new conditions. The genomic expression program required for maintenance of the optimal internal milieu in one environment may be far from optimal in a different environment. Yeasts regularly withstand fluctuations in the types and quantities of available nutrients, temperature, osmolarity and acidity of their environment, and the variable presence of noxious agents such as radiation and toxic chemicals. Whereas multicellular organisms can use specialized organs and tissues to provide a relatively stable and homogenous internal environment, unicellular organisms such as the yeast Saccharomyces cerevisiae have evolved autonomous mechanisms for adapting to drastic environmental changes. Myriad strategies have evolved to maintain these internal conditions in the face of variable and often harsh external environments. Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell.Ĭellular organisms require specific internal conditions for optimal growth and function. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators. Additional features of the genomic responses were specialized for specific conditions. A large set of genes (∼ 900) showed a similar drastic response to almost all of these environmental changes. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions.
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