Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis.
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.
Molecular Cancer Research, University Medical Centre Utrecht, Utrecht, the Netherlands.
Eva
E
Apweiler
Katrin
K
Sameith
Thanasis
T
Margaritis
Nathalie
N
Brabers
Loes
L
van de Pasch
Linda V
LV
Bakker
Dik
D
van Leenen
Frank Cp
FC
Holstege
Patrick
P
Kemmeren
D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014199:Trehalose / Q000378:metabolism*
D029701:Saccharomyces cerevisiae Proteins; C532521:TSL1 protein, S cerevisiae; D014199:Trehalose; D005964:Glucosyltransferases; C099692:trehalose synthase; D005947:Glucose