Metabolic intermediates selectively stimulate transcription factor interaction and modulate phosphate and purine pathways
- Benoît Pinson1,2,
- Sabine Vaur1,2,
- Isabelle Sagot1,2,
- Fanny Coulpier3,
- Sophie Lemoine3 and
- Bertrand Daignan-Fornier1,2,4
- 1Université de Bordeaux, Institut de Biochimie et Génétique Cellulaires, Bordeaux 33076, France;
- 2CNRS, UMR5095, Bordeaux, 33077 Cedex, France;
- 3IFR36, Plate-forme Transcriptome, École Normale Supérieure, Paris 75230, France
Abstract
Cells use strategic metabolites to sense the metabolome and accordingly modulate gene expression. Here, we show that the purine and phosphate pathways are positively regulated by the metabolic intermediate AICAR (5′-phosphoribosyl-5-amino-4-imidazole carboxamide). The transcription factor Pho2p is required for up-regulation of all AICAR-responsive genes. Accordingly, the binding of Pho2p to purine and phosphate pathway gene promoters is enhanced upon AICAR accumulation. In vitro, AICAR binds both Pho2p and Pho4p transcription factors and stimulates the interaction between Pho2p and either Bas1p or Pho4p in vivo. In contrast, SAICAR (succinyl-AICAR) only affects Pho2p–Bas1p interaction and specifically up-regulates purine regulon genes. Together, our data show that Bas1p and Pho4p compete for Pho2p binding, hence leading to the concerted regulation of cellular nucleotide synthesis and phosphate consumption.
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Footnotes
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↵4 Corresponding author.
E-MAIL B.Daignan-Fornier{at}ibgc.u-bordeaux2.fr; FAX 33-5-56-99-90-55.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.521809.
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Supplemental material is available at http://www.genesdev.org.
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- Received January 12, 2009.
- Accepted April 29, 2009.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press