Dynamic Transcriptional and Metabolic Responses in Yeast Adapting to Temperature Stress

Abstract

Understanding the response processes in cellular systems to external perturbations is a central goal of large-scale molecular profiling experiments. We investigated the molecular response of yeast to increased and lowered temperatures relative to optimal reference conditions across two levels of molecular organization: the transcriptome using a whole yeast genome microarray and the metabolome applying the gas chromatography=mass spectrometry (GC=MS) technology with in vivo stable-isotope labeling for accurate relative quantification of a total of 50 different metabolites. The molecular adaptation of yeast to increased or lowered temperatures relative control conditions at both the metabolic and transcriptional level is dominated by temperature-inverted differential regulation patterns of transcriptional and metabolite responses and the temporal response observed to be biphasic. The set of previously described general environmental stress response (ESR) genes showed particularly strong temperature-inverted response patterns. Among the metabolites measured, trehalose was detected to respond strongest to the temperature stress and with temperature-inverted up-and downregulation relative to control, midtemperature conditions. Although associated with the same principal environmental parameter, the two different temperature regimes caused very distinct molecular response patterns at both the metabolite and the transcript level. While pairwise correlations between different transcripts and between different metabolites were found generally preserved under the various conditions, substantial differences were also observed indicative of changed underlying network architectures or modified regulatory relationships. Gene and associated gene functions were identified that are differentially regulated specifically under the gradual stress induction applied here compared to abrupt stress exposure investigated in previous studies, including genes of as of yet unidentified function and genes involved in protein synthesis and energy metabolism.

Metabolic Pathway Relationships Revealed by an Integrative Analysis of the Transcriptional and Metabolic Temperature Stress-Response Dynamics in Yeast

“…Transcript and metabolite profiling data were taken from a series of temperature-stress response experiments in Saccharomyces cerevisiae exposed to gradually introduced heat (378C) or cold (108C) conditions relative to optimal-growth control conditions (288C) (Strassburg et al, 2010). Time series data covering 7 time points (0 min, 15 min, 30 min, 1 h, 2 h, 4 h, and 8 h) corresponding to the three different conditions (heat, cold, and control) were available for analysis.…”

“…Time series data covering 7 time points (0 min, 15 min, 30 min, 1 h, 2 h, 4 h, and 8 h) corresponding to the three different conditions (heat, cold, and control) were available for analysis. The 24-h time point was not considered in the analysis as it was determined to correspond to a different growth phase and not associated directly with the immediate stress response (Strassburg et al, 2010).…”

“…Thirty-six metabolites were detected under all experimental conditions (26 of those annotated). A total of 42 metabolites were detected in the heat stress (28 annotated), and 44 were found in cold stressed samples (31 annotated) (Strassburg et al, 2010). In all analyses requiring metabolic pathway information (see below) and thus a mapping of metabolites to metabolic pathway maps, all nonannotated metabolites have been ignored.…”

“…Detailed information on metabolite data generation and processing can be found in Strassburg et al (2010). The Affymetrix probeset data as provided in CEL file format and was subjected to quantile 262 WALTHER ET AL.…”

“…In this study, we analyzed transcriptomics and metabolomics time-series data obtained from yeast responding to heat and cold temperature stress (Strassburg et al, 2010). Specifically, we wished to assess the information contents of the two different molecular systems levels with regard to pathway relationship inference.…”