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Regenberg, Birgitte; Grotkjær, Thomas; Winther, Ole; Fausbøll, Anders; Åkesson, Mats; Bro, Christoffer; Hansen, Lars Kai; Brunak, Søren; Nielsen, Jens

doi:10.1186/gb-2006-7-11-r107

Cited by 211 publications

(142 citation statements)

References 58 publications

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“…Growth-rate dependent control of gene expression was implied also in the regulation of gene expression in the budding yeast [18]. The dependence of gene expression on growth rate was characterized most comprehensively using continuous chemostat cultures growing at steady state [18].…”

Section: Introductionmentioning

confidence: 99%

“…The dependence of gene expression on growth rate was characterized most comprehensively using continuous chemostat cultures growing at steady state [18]. A large multitude of genes exhibited an expression pattern that was strongly correlated with growth rate.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, ribosomal biogenesis gene expression increased with increasing growth rate, whereas the expression of stress-related genes decreased. Based on the genomic distribution of growth-correlated genes, it was suggested that growth-rate dependence is achieved through replication-mediated changes in chromatin modification [18]. In the context of the internal vs. external regulatory strategies discussed above, however, the interpretation of the observed correlations is difficult, since changes in growth rate necessarily involved change in the amount of the limiting factor (glucose) in the medium.…”

Section: Introductionmentioning

confidence: 99%

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Strategy of Transcription Regulation in the Budding Yeast

et al. 2007

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Cells must adjust their gene expression in order to compete in a constantly changing environment. Two alternative strategies could in principle ensure optimal coordination of gene expression with physiological requirements. First, characters of the internal physiological state, such as growth rate, metabolite levels, or energy availability, could be feedback to tune gene expression. Second, internal needs could be inferred from the external environment, using evolutionary-tuned signaling pathways. Coordination of ribosomal biogenesis with the requirement for protein synthesis is of particular importance, since cells devote a large fraction of their biosynthetic capacity for ribosomal biogenesis. To define the relative contribution of internal vs. external sensing to the regulation of ribosomal biogenesis gene expression in yeast, we subjected S. cerevisiae cells to conditions which decoupled the actual vs. environmentally-expected growth rate. Gene expression followed the environmental signal according to the expected, but not the actual, growth rate. Simultaneous monitoring of gene expression and growth rate in continuous cultures further confirmed that ribosome biogenesis genes responded rapidly to changes in the environments but were oblivious to longer-term changes in growth rate. Our results suggest that the capacity to anticipate and prepare for environmentally-mediated changes in cell growth presented a major selection force during yeast evolution.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Strategy of Transcription Regulation in the Budding Yeast

et al. 2007

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“…In batch cultures, the tight coupling of temperature and specific growth rate makes it exceedingly difficult to dissect effects of these two parameters. For example, it is well documented that, even at a fixed growth temperature, different specific growth rates result in different gene expression patterns (14) as well as different intracellular metabolite concentrations (15). In the present study, we circumvent this problem by comparing growth of S. cerevisiae at 12 and 30°C in glucose-limited chemostat cultures.…”

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confidence: 96%

Control of the Glycolytic Flux in Saccharomyces cerevisiae Grown at Low Temperature

Tai

Daran‐Lapujade

Luttik

et al. 2007

Journal of Biological Chemistry

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Growth temperature has a profound impact on the kinetic properties of enzymes in microbial metabolic networks. Activities of glycolytic enzymes in Saccharomyces cerevisiae were up to 7.5-fold lower when assayed at 12°C than at 30°C. Nevertheless, the in vivo glycolytic flux in chemostat cultures (dilution rate: 0.03 h ؊1 ) grown at these two temperatures was essentially the same. To investigate how yeast maintained a constant glycolytic flux despite the kinetic challenge imposed by a lower growth temperature, a systems approach was applied that involved metabolic flux analysis, transcript analysis, enzyme activity assays, and metabolite analysis. Expression of hexosetransporter genes was affected by the growth temperature, as indicated by differential transcription of five HXT genes and changed zero trans-influx kinetics of [ 14 C]glucose transport. No such significant changes in gene expression were observed for any of the glycolytic enzymes. Fermentative capacity (assayed off-line at 30°C), which was 2-fold higher in cells grown at 12°C, was therefore probably controlled predominantly by glucose transport. Massive differences in the intracellular concentrations of nucleotides (resulting in an increased adenylate energy charge at low temperature) and glycolytic intermediates indicated a dominant role of metabolic control as opposed to gene expression in the adaptation of glycolytic enzyme activity to different temperatures. In evolutionary terms, this predominant reliance on metabolic control of a central pathway, which represents a significant fraction of the cellular protein of the organism, may be advantageous to limit the need for protein synthesis and degradation during adaptation to diurnal temperature cycles.Changing ambient temperature, for example, as a result of diurnal temperature cycling, is among the most common environmental changes that microorganisms have to contend with in nature. Temperature effects on microbial physiology are also relevant for the industrial exploitation of microorganisms. For example, the temperature in industrial processes for production of alcoholic beverages with the yeast Saccharomyces cerevisiae (commonly 8 -20°C) is much lower than the optimum temperature range for growth (25-30°C) (1).Much of the current knowledge on adaptation of the model eukaryote S. cerevisiae to suboptimal temperatures has been derived from studies on cold shock. These studies have identified cold-induced changes in membrane lipid composition (2), transport functions, translational efficiency, protein folding, and nucleic acid structure (for a review, see Ref.3). Transcriptome analysis of cold adaptation in S. cerevisiae has revealed several types of responses that depend on the temperature range applied, namely "cold shock" (between 20 and 10°C) (4, 5) and "near freezing" (Ͻ10°C) (6) conditions. Responses to low temperature are also affected by the exposure period to low temperature (early phase and late phase responses (4, 6)). The early response in cold shock experiments encompasses upregulati...

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“…Using chemostats in combination with global analytical methods allows investigation of how the rate of growth impacts fundamental processes in the cell and conversely how the cell regulates and coordinates cellular process with its rate of growth. Studies in wildtype cells have shown that cellular concentrations of RNA and protein are profoundly impacted by rates of cell growth 6 and more recently it has been shown that transcriptome 10,12,13 and metabolome 8 are dramatically impacted by cell growth rates.…”

Section: Discussionmentioning

confidence: 99%

The Use of Chemostats in Microbial Systems Biology

Ziv

Brandt

Gresham

2013

JoVE

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Cells regulate their rate of growth in response to signals from the external world. As the cell grows, diverse cellular processes must be coordinated including macromolecular synthesis, metabolism and ultimately, commitment to the cell division cycle. The chemostat, a method of experimentally controlling cell growth rate, provides a powerful means of systematically studying how growth rate impacts cellular processes -including gene expression and metabolism -and the regulatory networks that control the rate of cell growth. When maintained for hundreds of generations chemostats can be used to study adaptive evolution of microbes in environmental conditions that limit cell growth. We describe the principle of chemostat cultures, demonstrate their operation and provide examples of their various applications. Following a period of disuse after their introduction in the middle of the twentieth century, the convergence of genome-scale methodologies with a renewed interest in the regulation of cell growth and the molecular basis of adaptive evolution is stimulating a renaissance in the use of chemostats in biological research. Video LinkThe video component of this article can be found at

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Abstract: Analysis of S. cerevisiae cultures with generation times varying between 2 and 35 hours shows that the expression of half of all yeast genes is affected by the specific growth rate.

Cited by 211 publications

References 58 publications

Strategy of Transcription Regulation in the Budding Yeast

Strategy of Transcription Regulation in the Budding Yeast

Control of the Glycolytic Flux in Saccharomyces cerevisiae Grown at Low Temperature

The Use of Chemostats in Microbial Systems Biology

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