Two-dimensional transcriptome analysis in chemostat cultures. Combinatorial effects of oxygen availability and macronutrient limitation in Saccharomyces cerevisiae.

Genome-wide analysis of transcriptional regulation is generally studied by determining sets of "signature transcripts" that are up- or down-regulated relative to a reference situation when a single culture parameter or genetic modification is changed. This approach is especially relevant for defining small subsets of transcripts for use in high throughput, cost-effective diagnostic analyses. However, this approach may overlook the simultaneous control of transcription by more than one environmental parameter. This study represents the first quantitative assessment of the impact of transcriptional cross-regulation by different environmental parameters. As a model, we compared the response of aerobic as well as anaerobic chemostat cultures of the yeast Saccharomyces cerevisiae to growth limitation by four different macronutrients (carbon, nitrogen, phosphorus, and sulfur). The identity of the growth-limiting nutrient was shown to have a strong impact on the sets of transcripts that responded to oxygen availability and vice versa. We concluded that identification of reliable signature transcripts for specific environmental parameters can be obtained only by combining transcriptome data sets obtained under several sets of reference conditions. Furthermore, the two-dimensional approach to transcriptome analysis is a valuable new tool to study the interaction of different transcriptional regulation systems.