Regulation of gene expression by a metabolic enzyme.
Gene expression in eukaryotes is normally believed to be controlled by transcriptional regulators that activate genes encoding structural proteins and enzymes. To identify previously unrecognized DNA binding activities, a yeast proteome microarray was screened with DNA probes; Arg5,6, a well-characterized mitochondrial enzyme involved in arginine biosynthesis, was identified. Chromatin immunoprecipitation experiments revealed that Arg5,6 is associated with specific nuclear and mitochondrial loci in vivo, and Arg5,6 binds to specific fragments in vitro. Deletion of Arg5,6 causes altered transcript levels of both nuclear and mitochondrial target genes. These results indicate that metabolic enzymes can directly regulate eukaryotic gene expression.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8005, USA.
David A
DA
Hall
Heng
H
Zhu
Xiaowei
X
Zhu
Thomas
T
Royce
Mark
M
Gerstein
Michael
M
Snyder
D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D003470:Culture Media; D015342:DNA Probes; D004271:DNA, Fungal / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D007438:Introns; D009097:Multienzyme Complexes / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017851:Phosphotransferases (Carboxyl Group Acceptor) / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D020543:Proteome; D012331:RNA, Fungal / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D014158:Transcription, Genetic
C492864:Arg5,6 protein, S cerevisiae; D003470:Culture Media; D015342:DNA Probes; D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D004277:DNA, Single-Stranded; D009097:Multienzyme Complexes; D020543:Proteome; D012331:RNA, Fungal; D011993:Recombinant Fusion Proteins; D000445:Aldehyde Oxidoreductases; D017851:Phosphotransferases (Carboxyl Group Acceptor)