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Lee, SS, Kennedy, S, Tolonen, AC and Ruvkun, G (2003) DAF-16 target genes that control C. elegans life-span and metabolism. Science 300:644-7
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.
Animals; Binding Sites; Caenorhabditis/genetics; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans/physiology; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/physiology; Computational Biology; Conserved Sequence; Down-Regulation; Drosophila/genetics; Gene Expression Profiling; Gene Expression Regulation; Genes, Helminth; Genes, Insect; Genomics; Insulin/metabolism; Longevity/genetics; Mutation; Promoter Regions, Genetic; RNA Interference; Receptor, Insulin/genetics; Receptor, Insulin/metabolism; Signal Transduction; Transcription Factors/genetics; Transcription Factors/physiology; Up-Regulation
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