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Open Access Research

Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae

Birgitte Regenberg1, Thomas Grotkjær2, Ole Winther3, Anders Fausbøll4, Mats Åkesson2, Christoffer Bro2, Lars Kai Hansen3, Søren Brunak4 and Jens Nielsen2*

Author Affiliations

1 Institut für Molekulare Biowissenschaften, Johann Wolfgang Goethe-Universität, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany

2 Center for Microbial Biotechnology, BioCentrum-DTU, 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, BioCentrum-DTU, Building 208, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark

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Genome Biology 2006, 7:R107  doi:10.1186/gb-2006-7-11-r107

Published: 14 November 2006

Abstract

Background

Growth rate is central to the development of cells in all organisms. However, little is known about the impact of changing growth rates. We used continuous cultures to control growth rate and studied the transcriptional program of the model eukaryote Saccharomyces cerevisiae, with generation times varying between 2 and 35 hours.

Results

A total of 5930 transcripts were identified at the different growth rates studied. Consensus clustering of these revealed that half of all yeast genes are affected by the specific growth rate, and that the changes are similar to those found when cells are exposed to different types of stress (>80% overlap). Genes with decreased transcript levels in response to faster growth are largely of unknown function (>50%) whereas genes with increased transcript levels are involved in macromolecular biosynthesis such as those that encode ribosomal proteins. This group also covers most targets of the transcriptional activator RAP1, which is also known to be involved in replication. A positive correlation between the location of replication origins and the location of growth-regulated genes suggests a role for replication in growth rate regulation.

Conclusion

Our data show that the cellular growth rate has great influence on transcriptional regulation. This, in turn, implies that one should be cautious when comparing mutants with different growth rates. Our findings also indicate that much of the regulation is coordinated via the chromosomal location of the affected genes, which may be valuable information for the control of heterologous gene expression in metabolic engineering.