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Science 300 (5619): 644-647

Copyright © 2003 by the American Association for the Advancement of Science

DAF-16 Target Genes That Control C. elegans Life-Span and Metabolism

Siu Sylvia Lee,1 Scott Kennedy,1 Andrew C. Tolonen,2 Gary Ruvkun1*

Abstract: Signaling from the DAF-2/insulin receptor to the DAF-16/FOXO transcription factor controls longevity, metabolism, and development in disparate phyla. To identify genes that mediate the conserved biological outputs of daf-2/insulin-like signaling, we usedcomparative genomics to identify 17 orthologous genes from Caenorhabditis and Drosophila, each of which bears a DAF-16 binding site in the promoter region. One-third of these DAF-16 downstream candidate genes were regulatedby daf-2/insulin-like signaling in C. elegans, and RNA interference inactivation of the candidates showed that many of these genes mediate distinct aspects of daf-16 function, including longevity, metabolism, anddevelopment.

1 Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, 50 Blossom Street, Boston, MA 02114, USA.
2 Department of Biology, Massachusetts Institute of Technology, 15 Vassar Street, Building 48-424, Cambridge, MA 02139, USA.

* To whom correspondence should be addressed. E-mail: ruvkun{at}molbio.mgh.harvard.edu


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