Project description:Life is resilient because living systems are able to respond to elevated temperatures with an ancient gene expression program called the heat shock response (HSR). Our global analysis revealed a modular HSR dependent on the severity of the stress in yeast. Interestingly, at all temperatures analyzed, the transcription of hundreds of genes is upregulated among them the molecular chaperones, which protect proteins from aggregation. However, for approximately 90% of the regulated genes, the function under stress remained enigmatic. Surprisingly, the majority of these upregulated genes is translated but only for a small fraction this results in raised proteins levels. In this context, increased translation is required to counter-balance elevated protein turnover at elevated temperatures. This anaplerotic reaction together with the molecular chaperone system allows yeast to buffer proteotoxic stress. When the capacity of this system is exhausted at extreme temperatures, translation is stopped via phase transition and growth stops.
Project description:Yeast Saccharomyces cerevisiae has been widely used as a model system for studying genomic instability. In this study, heat-shock-induced genomic alterations were explored in the heterozygous diploid yeast strain JSC25-1. In combination of the whole-genome microarray, the patterns of chromosomal instability induced by heat shock could also be explored at a whole genome level. Using this system, we found heat-shock treatment resulted in hundreds-fold higher rate of genomic alterations, including aneuploidy and loss of heterozygosity (LOH).
Project description:Microarray time courses followed the response of 5 yeast strains to heat shock. Expression variation due to genetic, environmental, and genotype-by-environment interactions were identified. Keywords: Timecourse and single timepoint expression studies of stress response in yeast
Project description:Microarray time courses followed the response of 5 yeast strains to heat shock. Expression variation due to genetic, environmental, and genotype-by-environment interactions were identified. Keywords: Timecourse and single timepoint expression studies of stress response in yeast The genomic expression response to heat shock was measured in 5 different yeast strains over the course of 2 hours. Basal expression at 25C was also compared in 4 non-lab strains to the S288c refernce. All experiments were done in duplicate, for a total of 68 Samples.
Project description:CRISPRi screens on the repression of 129 protein kinases and 161 transcription factors in S. cerevisiae. We quantify perturbation effects on cellular fitness at 23, 30 and 38°C, expression of the SSA1 Hsp70 chaperone (as proxy for heat shock response activity) and thermotolerance. The integration of these phenotypes allowed us to identify core signaling pathways of the HSR and their contributions to temperature-associated growth and heat resistance.
Project description:<p>Gene expression is a biological process regulated at different molecular levels, including chromatin accessibility, transcription, and RNA maturation and transport. In addition, these regulatory mechanisms have strong links with cellular metabolism. Here we present a multi-omics dataset that captures different aspects of this multi-layered process in yeast. We obtained RNA-seq, metabolomics, and H4K12Ac ChIP-seq data for wild-type and mip6delta strains during a heat-shock time course. Mip6 is an RNA-binding protein that contributes to RNA export during environmental stress and is informative of the contribution of post-transcriptional regulation to control cellular adaptations to environmental changes. The experiment was performed in quadruplicate, and the different omics measurements were obtained from the same biological samples, which facilitates the integration and analysis of data using covariance-based methods. We validate our dataset by showing that ChIP-seq, RNA-seq and metabolomics signals recapitulate existing knowledge about the response of ribosomal genes and the contribution of trehalose metabolism to heat stress.</p>
Project description:S. cerevisiae cells acidify when they experience stressful temperatures. In addition, newly-translated proteins are thought to misfold, triggering the heat shock response. To determine whether heat-shock associated acidification and translation state are important for the cellular response, we manipulated intracellular pH, blocked translation, heat shocked cells, and sequenced the transcriptome.