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PMID: 11390663 Published · ppublish English Journal Article

Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast.

Molecular and cellular biology ·Vol. 21 ·No. 13 ·2001-07-00 ·Pages 4347-68

Natarajan K, Meyer MR, Jackson BM, Slade D, Roberts C, Hinnebusch AG, Marton MJ

Abstract

Starvation for amino acids induces Gcn4p, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. In an effort to identify all genes regulated by Gcn4p during amino acid starvation, we performed cDNA microarray analysis. Data from 21 pairs of hybridization experiments using two different strains derived from S288c revealed that more than 1,000 genes were induced, and a similar number were repressed, by a factor of 2 or more in response to histidine starvation imposed by 3-aminotriazole (3AT). Profiling of a gcn4Delta strain and a constitutively induced mutant showed that Gcn4p is required for the full induction by 3AT of at least 539 genes, termed Gcn4p targets. Genes in every amino acid biosynthetic pathway except cysteine and genes encoding amino acid precursors, vitamin biosynthetic enzymes, peroxisomal components, mitochondrial carrier proteins, and autophagy proteins were all identified as Gcn4p targets. Unexpectedly, genes involved in amino acid biosynthesis represent only a quarter of the Gcn4p target genes. Gcn4p also activates genes involved in glycogen homeostasis, and mutant analysis showed that Gcn4p suppresses glycogen levels in amino acid-starved cells. Numerous genes encoding protein kinases and transcription factors were identified as targets, suggesting that Gcn4p is a master regulator of gene expression. Interestingly, expression profiles for 3AT and the alkylating agent methyl methanesulfonate (MMS) overlapped extensively, and MMS induced GCN4 translation. Thus, the broad transcriptional response evoked by Gcn4p is produced by diverse stress conditions. Finally, profiling of a gcn4Delta mutant uncovered an alternative induction pathway operating at many Gcn4p target genes in histidine-starved cells.

MeSH Terms
Amino Acids/biosynthesis,genetics Amitrole/pharmacology DNA-Binding Proteins/genetics,metabolism Fungal Proteins/genetics,metabolism Gene Expression Profiling Gene Expression Regulation, Fungal/genetics Genes, Reporter/genetics Glycogen/metabolism Methyl Methanesulfonate/pharmacology Mitochondria/genetics,metabolism Models, Theoretical Mutagens/pharmacology Oligonucleotide Array Sequence Analysis Peroxisomes/genetics,metabolism Promoter Regions, Genetic/genetics Protein Kinases/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Saccharomyces cerevisiae/genetics,physiology Saccharomyces cerevisiae Proteins Trans-Activators/genetics,metabolism
Chemicals
Amino Acids DNA-Binding Proteins Fungal Proteins Mutagens Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Trans-Activators Glycogen Methyl Methanesulfonate Protein Kinases Amitrole
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Natarajan K
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Meyer M R
Jackson B M
Slade D
Roberts C
Hinnebusch A G
Marton M J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.13.4347-4368.2001
Published
2001-07-00
Pages
4347-68
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC87095
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.13.4347-4368.2001 PMC Full Text View journal details
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