title: Gcn4p and the Crabtree effect of yeast: drawing the causal model of the Crabtree effect in Saccharomyces cerevisiae and explaining evolutionary trade-offs of adaptation to galactose through systems biology.
abstract: By performing an integrated comparative analysis on the physiology and transcriptome of four different S. cerevisiae strains growing on galactose and glucose, it was inferred that the transcription factors Bas1p, Pho2p, and Gcn4p play a central role in the regulatory events causing the Crabtree effect in S. cerevisiae. The analysis also revealed that a point mutation in the RAS2 observed in a galactose-adapted strain causes a lower Crabtree effect and growth rate on glucose by decreasing the activity of Gcn4p while at the same time is at the origin of higher growth rate on galactose due to a lower activity of the transcriptional repressor Sok2p. The role of Gcn4p on the trade-off effect observed on glucose was confirmed experimentally. This was done by showing that the point mutation in RAS2 does not result in a lower growth rate on glucose if it is introduced in a GCN4-negative background.
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: José L
authors.initials: JL
authors.lastname: Martínez
authors.forename: Sergio
authors.initials: S
authors.lastname: Bordel
authors.forename: KuFk-Ki
authors.initials: KK
authors.lastname: Hong
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D000222:Adaptation, Physiological; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism*; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D049490:Systems Biology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: C061767:BAS1 protein, S cerevisiae; D050976:Basic-Leucine Zipper Transcription Factors; C501391:GCN4 protein, S cerevisiae; D018398:Homeodomain Proteins; C051611:PHO2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D005947:Glucose; D005690:Galactose
keywords: Bas1; Crabtree effect; Gcn4; flux analysis; random sampling