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Science 306 (5695): 482-484

Copyright © 2004 by the American Association for the Advancement of Science

Regulation of Gene Expression by a Metabolic Enzyme

David A. Hall,1 Heng Zhu,2* Xiaowei Zhu,3 Thomas Royce,1 Mark Gerstein,1 Michael Snyder1,2{dagger}

Abstract: 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.

1 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520–8005, USA.
2 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520–8005, USA.
3 Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520–8005, USA.

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* Present address: Department of Pharmacology and the High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

{dagger} To whom the correspondence should be addressed. E-mail: michael.snyder{at}

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