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Science. 2003 Apr 25;300(5619):644-7. Epub 2003 Apr 10.

DAF-16 target genes that control C. elegans life-span and metabolism.

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Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, 50 Blossom Street, Boston, MA 02114, USA.


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 used comparative 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 regulated by 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, and development.

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