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Title: Unraveling condition-dependent networks of transcription factors that control metabolic pathway activity in yeast
Authors: Fendt, Sarah-Maria
Oliveira, Ana Paula
Christen, Stefan
Picotti, Paola
Dechant, Reinhard Christoph
Sauer, Uwe # ×
Issue Date: Nov-2010
Publisher: Nature Pub. Group
Series Title: Molecular Systems Biology vol:6 pages:432
Article number: 10.1038/msb.2010.91
Abstract: Which transcription factors control the distribution of metabolic fluxes under a given condition? We address this question by systematically quantifying metabolic fluxes in 119 transcription factor deletion mutants of Saccharomyces cerevisiae under five growth conditions. While most knockouts did not affect fluxes, we identified 42 condition-dependent interactions that were mediated by a total of 23 transcription factors that control almost exclusively the cellular decision between respiration and fermentation. This relatively sparse, condition-specific network of active metabolic control contrasts with the much larger gene regulation network inferred from expression and DNA binding data. Based on protein and transcript analyses in key mutants, we identified three enzymes in the tricarboxylic acid cycle as the key targets of this transcriptional control. For the transcription factor Gcn4, we demonstrate that this control is mediated through the PKA and Snf1 signaling cascade. The discrepancy between flux response predictions, based on the known regulatory network architecture and our functional (13)C-data, demonstrates the importance of identifying and quantifying the extent to which regulatory effectors alter cellular functions.
URI: 
ISSN: 1744-4292
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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