title: The SAGA histone acetyltransferase complex regulates leucine uptake through the Agp3 permease in fission yeast.
abstract: Metabolic responses of unicellular organisms are mostly acute, transient, and cell-autonomous. Regulation of nutrient uptake in yeast is one such rapid response. High quality nitrogen sources such as NH(4)(+) inhibit uptake of poor nitrogen sources, such as amino acids. Both transcriptional and posttranscriptional mechanisms operate in nutrient uptake regulation; however, many components of this system remain uncharacterized in the fission yeast, Schizosaccharomyces pombe. Here, we demonstrate that the Spt-Ada-Gcn acetyltransferase (SAGA) complex modulates leucine uptake. Initially, we noticed that a branched-chain amino acid auxotroph exhibits a peculiar adaptive growth phenotype on solid minimal media containing certain nitrogen sources. In fact, the growth of many auxotrophic strains is inhibited by excess NH(4)Cl, possibly through nitrogen-mediated uptake inhibition of the corresponding nutrients. Surprisingly, DNA microarray analysis revealed that the transcriptional reprogramming during the adaptation of the branched-chain amino acid auxotroph was highly correlated with reprogramming observed in deletions of the SAGA histone acetyltransferase module genes. Deletion of gcn5(+) increased leucine uptake in the prototrophic background and rendered the leucine auxotroph resistant to NH(4)Cl. Deletion of tra1(+) caused the opposite phenotypes. The increase in leucine uptake in the gcn5Δ mutant was dependent on an amino acid permease gene, SPCC965.11c(+). The closest budding yeast homolog of this permease is a relatively nonspecific amino acid permease AGP3, which functions in poor nutrient conditions. Our analysis identified the regulation of nutrient uptake as a physiological function for the SAGA complex, providing a potential link between cellular metabolism and chromatin regulation.
authors.affiliation: Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Sun
authors.forename: Makiko
authors.initials: M
authors.lastname: Hamamoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yashiroda
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D020869:Gene Expression Profiling; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D000637:Transaminases / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000643:Ammonium Chloride; D003470:Culture Media; D007930:Leucine; D029702:Schizosaccharomyces pombe Proteins; D000637:Transaminases; C577536:SPCC965.11c protein, S pombe; C501322:Gcn5 protein, S pombe; D000099224:p300-CBP-Associated Factor; C019798:branched-chain-amino-acid transaminase