Project description:Timely signaling pathways activation allows cells to survive diverse environmental stress conditions. Mitogen-activated protein kinases (MAPKs) are a highly conserved class of signaling molecules in eukaryotes with essential functions in cellular responses to stress. In Saccharomyces cerevisiae, the role of MAPK Hog1 as a master regulator of the coordinated response to osmotic stress is well understood. However, recent findings suggest that the role of Hog1 may extend beyond canonical osmoadaptation. This study investigates the role of Hog1 in mediating transcriptional responses to acute oxidative and ethanol stress. By harnessing the natural variation present in wild strains of S. cerevisiae, we use gene knockouts, comparative transcriptomics, and survival assays to determine Hog1’s involvement in stress responses beyond osmoadaptation. Our findings demonstrate that Hog1 mediates transcriptional reprogramming for non-osmotic stress response in a strain-dependent manner. Osmospecificity of Hog1 activity was identified in the DBY8268 laboratory strain, while differential gene expression was observed in HOG1 knockouts of all wild strains tested under both oxidative and ethanol stress. Further, our data indicate that the function of Hog1 in the response to non-osmotic stress is distinct from the canonical response, with effects ranging from altered ribosomal protein expression dynamics to altered environmental stress response (ESR) activity. Differences in expression correlate with fitness defects of hog1∆ mutants. These results suggest a generalized role of the Hog1 MAPK in S. cerevisiae, consistent with an evolutionarily generalized function for this kinase, underscoring the importance of genomic diversity for elucidating stress signalling dynamics in yeast.
Project description:Cells regulate gene expression using a complex network of signaling pathways, transcription factors and promoters. To gain insight into the structure and function of these networks we analyzed gene expression in single and multiple mutant strains to build a quantitative model of the Hog1 MAPK-dependent osmotic stress response in budding yeast. Our model reveals that the Hog1 and general stress (Msn2/4) pathways interact, at both the signaling and promoter level, to integrate information and create a context-dependent response. Keywords: Stress response network analysis using genetically modified cells 85 samples were used to dissect the structure and function of the Hog1 network (Critical Samples measured in triplicate). The overall strategy was to double mutant or epistasis analysis to break down the influence that genes in the Hog1 network have on each other and the genome-wide stress response. This was done by comparing the expression in strains with different combinations of genes deleted and fitting the data to quantitative models. See Capaldi et. al. Nature Genetics 2008 for details.
Project description:In our previous work, we had found that Saccharomyces cerevisiae needs of the Hog1 and Slt2 proteins to growth in a low pH environment caused by sulfuric acid, one of the stress factors during the process of ethanol production. Then was performed the gene-wide expression analysis in the hog1∆ and slt2∆ mutants in order to reveal the function of the Hog1p and Slt2p MAP Kinases in the regulation of S. cerevisiae global gene expression upon stress by sulfuric acid.
Project description:Cells regulate gene expression using a complex network of signaling pathways, transcription factors and promoters. To gain insight into the structure and function of these networks we analyzed gene expression in single and multiple mutant strains to build a quantitative model of the Hog1 MAPK-dependent osmotic stress response in budding yeast. Our model reveals that the Hog1 and general stress (Msn2/4) pathways interact, at both the signaling and promoter level, to integrate information and create a context-dependent response. Keywords: Stress response network analysis using genetically modified cells