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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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Transcriptional regulation within the glucose regulatory system. Transcript changes (horizontal) of all essential pathway members, those that upon deletion still behave like WT (“like WT”), as well as transcripts of pathway members categorised into the “high glucose” and “low glucose” group are depicted in the different mutants (vertical). Grey boxes indicate pathway members involved in the metabolic pathways. Colour scale and order of mutants (vertical) as in Figure 2. Transcripts (horizontal) of essential pathway members and members corresponding to mutants that behave like WT are ordered as derived from the hierarchical clustering. The transcript ordering of pathway members included in the “high glucose” and “low glucose group” is the same as for the mutants. The diagonal depicts the deleted genes.
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Figure 4: Transcriptional regulation within the glucose regulatory system. Transcript changes (horizontal) of all essential pathway members, those that upon deletion still behave like WT (“like WT”), as well as transcripts of pathway members categorised into the “high glucose” and “low glucose” group are depicted in the different mutants (vertical). Grey boxes indicate pathway members involved in the metabolic pathways. Colour scale and order of mutants (vertical) as in Figure 2. Transcripts (horizontal) of essential pathway members and members corresponding to mutants that behave like WT are ordered as derived from the hierarchical clustering. The transcript ordering of pathway members included in the “high glucose” and “low glucose group” is the same as for the mutants. The diagonal depicts the deleted genes.

Mentions: The main transcriptional response (Figure 2) indicates a tight interconnection between the individual pathways of the glucose regulatory system. To investigate the degree to which components of the glucose regulatory system transcriptionally influence each other, the effect of deleting one pathway member on the mRNA expression of all the other pathway members was systematically determined (Figure 4). When assayed in this way, members of the Ras/PKA, Gpr1/PKA, Sch9, Yak1, Snf1 and Snf3/Rgt2 signalling pathways are only infrequently regulated at the mRNA level. In contrast, genes whose transcription is frequently changed encode members of the metabolic pathways (Figure 4, indicated by grey boxes; Supplementary Figure 2 in Additional file 3), especially enzymes involved in the biosynthesis of glycogen and trehalose. Their transcript levels are strongly increased in deletion mutants of the “high glucose” group (Figure 4, top) and decreased in deletion mutants of the “low glucose” group (Figure 4, bottom). With the exception of Gph1, Nth2, Tps2 and Tsl1, metabolic pathway members regulated at the level of transcription do not result in significant transcriptional changes upon their own deletion, most likely because their activity is not required under the high glucose conditions used in this study. Taken together, these analyses indicate that changes in perceived glucose levels ultimately lead to a shift in the metabolic programme, either to or from fermentation, and that this is achieved by regulating the transcription of metabolic pathway members, such as Gsy1, Gdb1, Tps2 and Tsl1.


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)

Transcriptional regulation within the glucose regulatory system. Transcript changes (horizontal) of all essential pathway members, those that upon deletion still behave like WT (“like WT”), as well as transcripts of pathway members categorised into the “high glucose” and “low glucose” group are depicted in the different mutants (vertical). Grey boxes indicate pathway members involved in the metabolic pathways. Colour scale and order of mutants (vertical) as in Figure 2. Transcripts (horizontal) of essential pathway members and members corresponding to mutants that behave like WT are ordered as derived from the hierarchical clustering. The transcript ordering of pathway members included in the “high glucose” and “low glucose group” is the same as for the mutants. The diagonal depicts the deleted genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Transcriptional regulation within the glucose regulatory system. Transcript changes (horizontal) of all essential pathway members, those that upon deletion still behave like WT (“like WT”), as well as transcripts of pathway members categorised into the “high glucose” and “low glucose” group are depicted in the different mutants (vertical). Grey boxes indicate pathway members involved in the metabolic pathways. Colour scale and order of mutants (vertical) as in Figure 2. Transcripts (horizontal) of essential pathway members and members corresponding to mutants that behave like WT are ordered as derived from the hierarchical clustering. The transcript ordering of pathway members included in the “high glucose” and “low glucose group” is the same as for the mutants. The diagonal depicts the deleted genes.
Mentions: The main transcriptional response (Figure 2) indicates a tight interconnection between the individual pathways of the glucose regulatory system. To investigate the degree to which components of the glucose regulatory system transcriptionally influence each other, the effect of deleting one pathway member on the mRNA expression of all the other pathway members was systematically determined (Figure 4). When assayed in this way, members of the Ras/PKA, Gpr1/PKA, Sch9, Yak1, Snf1 and Snf3/Rgt2 signalling pathways are only infrequently regulated at the mRNA level. In contrast, genes whose transcription is frequently changed encode members of the metabolic pathways (Figure 4, indicated by grey boxes; Supplementary Figure 2 in Additional file 3), especially enzymes involved in the biosynthesis of glycogen and trehalose. Their transcript levels are strongly increased in deletion mutants of the “high glucose” group (Figure 4, top) and decreased in deletion mutants of the “low glucose” group (Figure 4, bottom). With the exception of Gph1, Nth2, Tps2 and Tsl1, metabolic pathway members regulated at the level of transcription do not result in significant transcriptional changes upon their own deletion, most likely because their activity is not required under the high glucose conditions used in this study. Taken together, these analyses indicate that changes in perceived glucose levels ultimately lead to a shift in the metabolic programme, either to or from fermentation, and that this is achieved by regulating the transcription of metabolic pathway members, such as Gsy1, Gdb1, Tps2 and Tsl1.

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