Growth-dependent gene expression in Saccharomyces cerevisiae.
Birgitte Regenberg (1), Thomas Grotkjær (2), Ole Winther (3), Christoffer Bro (2), Jan von Köller (2), Anders Fausbøll (4), Mats Åkesson (5), Lars Kai Hansen (3), Jens Nielsen (2)
(1) Biozentrum, J. W. Goethe-Universität, Marie-Curie-Str. 9, Frankfurt am Main, 60439, Germany;
(2) Center for Microbial Biotechnology, Building 223 Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark;
(3) Informatics and Mathematical Modelling, Building 321 Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark;
(4) Center for Biological Sequence Analysis, Building 208 Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark;
(5) Novo Nordisk A/S, BioProcess Laboratories, Novo Allé, DK-2880 Bagsværd, Denmark
We describe the whole-genome transcription profile from Saccharomyces cerevisiae cultured at six different growth rates. The growth rate was controlled in aerobic glucose limited chemostat with doubling times ranging from two to 35 hours. The 5,901 detectable transcripts were clustered multiple times with Mixture of Gaussians and a consensus solution was extracted from a matrix describing the co-occurrence of transcripts in the same clusters from every run. In contrast to the clusters obtained in single runs, consensus clustering gives very robust, reproducible results. Using this method, two thirds of the transcripts grouped into nine clusters of genes affected by the growth. Ribosomal protein genes and other genes involved in metabolism were overrepresented among genes that were up-regulated in response to faster growth. These genes were mostly found on chromosome I, X, XI, and XIII around the ARSs while down-regulated genes were largely excluded from these chromosomes. Down-regulated genes fell into several clusters with different decline in expression level as a function of decreasing doubling time, of which two contained a large fraction of stress response genes and chromatin silencing genes. Several clusters revealed a peak in the expression around the critical dilution rate where S. cerevisiae change from respiratory to respiro-fermentative metabolism. Genes in these clusters were involved in ribosome biogenesis, respiration, C2-carbon metabolism and cytokinesis.
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