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Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis.

Apweiler E, Sameith K, Margaritis T, Brabers N, van de Pasch L, Bakker LV, van Leenen D, Holstege FC, Kemmeren P - BMC Genomics (2012)

Bottom Line: In general, the mutations do not induce pathway-specific transcriptional responses.Epistasis analysis of tps2Δ double mutants supports this prediction.Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Cancer Research, University Medical Centre Utrecht, Utrecht, the Netherlands.

ABSTRACT

Background: Cellular glucose availability is crucial for the functioning of most biological processes. Our understanding of the glucose regulatory system has been greatly advanced by studying the model organism Saccharomyces cerevisiae, but many aspects of this system remain elusive. To understand the organisation of the glucose regulatory system, we analysed 91 deletion mutants of the different glucose signalling and metabolic pathways in Saccharomyces cerevisiae using DNA microarrays.

Results: In general, the mutations do not induce pathway-specific transcriptional responses. Instead, one main transcriptional response is discerned, which varies in direction to mimic either a high or a low glucose response. Detailed analysis uncovers established and new relationships within and between individual pathways and their members. In contrast to signalling components, metabolic components of the glucose regulatory system are transcriptionally more frequently affected. A new network approach is applied that exposes the hierarchical organisation of the glucose regulatory system.

Conclusions: The tight interconnection between the different pathways of the glucose regulatory system is reflected by the main transcriptional response observed. Tps2 and Tsl1, two enzymes involved in the biosynthesis of the storage carbohydrate trehalose, are predicted to be the most downstream transcriptional components. Epistasis analysis of tps2Δ double mutants supports this prediction. Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

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Relationships exposed through gene expression profiling. Transcript changes (FC) of two different deletion mutants are plotted against each other. Red dots indicate the deleted genes. (A) Transcript changes of the pfk27Δ and tsl1Δ mutants are highly correlated. (B) Transcriptional changes of the asc1Δ mutant are not negatively correlated to those of the gpr1Δ mutant suggesting that Asc1 does not inhibit Gpr1. (C) The deletion of RAM1 results in many more transcriptional changes than the deletion of RAS2. RAS1 is not shown as its deletion behaves like WT.
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Figure 3: Relationships exposed through gene expression profiling. Transcript changes (FC) of two different deletion mutants are plotted against each other. Red dots indicate the deleted genes. (A) Transcript changes of the pfk27Δ and tsl1Δ mutants are highly correlated. (B) Transcriptional changes of the asc1Δ mutant are not negatively correlated to those of the gpr1Δ mutant suggesting that Asc1 does not inhibit Gpr1. (C) The deletion of RAM1 results in many more transcriptional changes than the deletion of RAS2. RAS1 is not shown as its deletion behaves like WT.

Mentions: In addition to established relationships such as those described above, a number of previously uncharacterised relationships can be inferred from the gene expression profiles. The tight correlation observed between the gene expression profile of tsl1Δ and pfk27Δ (Figure 3A) is indicative of a functional relationship. This is further substantiated by their positive genetic interaction as derived from a high-throughput synthetic genetic interaction map [36], which can signify that both gene products are part of the same complex or pathway. Until now, no concrete role has been assigned to Tsl1 but it is speculated to have regulatory functions within the trehalose synthase complex [37]. Pfk27 is the 6-phosphofructo-2-kinase that synthesises the key metabolite fructose-2,6-bisphosphate, which regulates the glycolytic/gluconeogenic switch. The correlation between the tsl1Δ and pfk27Δ gene expression profiles indicates a regulatory link between storage carbohydrate synthesis and the shift from glycolysis to gluconeogenesis and vice versa.


Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis.

Apweiler E, Sameith K, Margaritis T, Brabers N, van de Pasch L, Bakker LV, van Leenen D, Holstege FC, Kemmeren P - BMC Genomics (2012)

Relationships exposed through gene expression profiling. Transcript changes (FC) of two different deletion mutants are plotted against each other. Red dots indicate the deleted genes. (A) Transcript changes of the pfk27Δ and tsl1Δ mutants are highly correlated. (B) Transcriptional changes of the asc1Δ mutant are not negatively correlated to those of the gpr1Δ mutant suggesting that Asc1 does not inhibit Gpr1. (C) The deletion of RAM1 results in many more transcriptional changes than the deletion of RAS2. RAS1 is not shown as its deletion behaves like WT.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472246&req=5

Figure 3: Relationships exposed through gene expression profiling. Transcript changes (FC) of two different deletion mutants are plotted against each other. Red dots indicate the deleted genes. (A) Transcript changes of the pfk27Δ and tsl1Δ mutants are highly correlated. (B) Transcriptional changes of the asc1Δ mutant are not negatively correlated to those of the gpr1Δ mutant suggesting that Asc1 does not inhibit Gpr1. (C) The deletion of RAM1 results in many more transcriptional changes than the deletion of RAS2. RAS1 is not shown as its deletion behaves like WT.
Mentions: In addition to established relationships such as those described above, a number of previously uncharacterised relationships can be inferred from the gene expression profiles. The tight correlation observed between the gene expression profile of tsl1Δ and pfk27Δ (Figure 3A) is indicative of a functional relationship. This is further substantiated by their positive genetic interaction as derived from a high-throughput synthetic genetic interaction map [36], which can signify that both gene products are part of the same complex or pathway. Until now, no concrete role has been assigned to Tsl1 but it is speculated to have regulatory functions within the trehalose synthase complex [37]. Pfk27 is the 6-phosphofructo-2-kinase that synthesises the key metabolite fructose-2,6-bisphosphate, which regulates the glycolytic/gluconeogenic switch. The correlation between the tsl1Δ and pfk27Δ gene expression profiles indicates a regulatory link between storage carbohydrate synthesis and the shift from glycolysis to gluconeogenesis and vice versa.

Bottom Line: In general, the mutations do not induce pathway-specific transcriptional responses.Epistasis analysis of tps2Δ double mutants supports this prediction.Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Cancer Research, University Medical Centre Utrecht, Utrecht, the Netherlands.

ABSTRACT

Background: Cellular glucose availability is crucial for the functioning of most biological processes. Our understanding of the glucose regulatory system has been greatly advanced by studying the model organism Saccharomyces cerevisiae, but many aspects of this system remain elusive. To understand the organisation of the glucose regulatory system, we analysed 91 deletion mutants of the different glucose signalling and metabolic pathways in Saccharomyces cerevisiae using DNA microarrays.

Results: In general, the mutations do not induce pathway-specific transcriptional responses. Instead, one main transcriptional response is discerned, which varies in direction to mimic either a high or a low glucose response. Detailed analysis uncovers established and new relationships within and between individual pathways and their members. In contrast to signalling components, metabolic components of the glucose regulatory system are transcriptionally more frequently affected. A new network approach is applied that exposes the hierarchical organisation of the glucose regulatory system.

Conclusions: The tight interconnection between the different pathways of the glucose regulatory system is reflected by the main transcriptional response observed. Tps2 and Tsl1, two enzymes involved in the biosynthesis of the storage carbohydrate trehalose, are predicted to be the most downstream transcriptional components. Epistasis analysis of tps2Δ double mutants supports this prediction. Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

Show MeSH