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Originally published In Press as doi:10.1074/jbc.M410573200 on October 20, 2004

J. Biol. Chem., Vol. 280, Issue 1, 437-447, January 7, 2005
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Two-dimensional Transcriptome Analysis in Chemostat Cultures

COMBINATORIAL EFFECTS OF OXYGEN AVAILABILITY AND MACRONUTRIENT LIMITATION IN SACCHAROMYCES CEREVISIAE*{boxs}

Siew Leng Tai{ddagger}, Viktor M. Boer{ddagger}, Pascale Daran-Lapujade{ddagger}, Michael C. Walsh§, Johannes H. de Winde{ddagger}, Jean-Marc Daran{ddagger}||, and Jack T. Pronk{ddagger}

From the {ddagger}Kluyver Laboratory of Biotechnology, Delft University of Technology, Julianalaan 67, 2628BC Delft, The Netherlands, §Heineken Technical Services, Research and Development, Burgemeester Smeetsweg 1, 2380BB Zoeterwoude, The Netherlands, and DSM Life Sciences, Division of Bakery Ingredients, Technology Cluster, 2600MA Delft, The Netherlands

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.

Received for publication, September 14, 2004 , and in revised form, October 20, 2004.

The complete data set has been submitted to the Genome Expression Omnibus Database (available at www.ncbi.nlm.nih.gov/geo/) under series GSE1723.

* The work performed in the Kluyver Centre for Genomics of Industrial Fermentation was supported by the Netherlands Genomics Initiative. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{boxs} The on-line version of this article (available at http://www.jbc.org) contains Supplemental Tables 1–6.

|| To whom correspondence should be addressed. Tel.: 31-15-278-2412; Fax: 31-15-278-2355; E-mail: j.m.daran{at}tnw.tudelft.nl.


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