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 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Binding Sites
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Caenorhabditis / genetics
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / physiology
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Computational Biology
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Conserved Sequence
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Down-Regulation
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Drosophila / genetics
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Forkhead Transcription Factors
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Gene Expression Profiling
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Gene Expression Regulation
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Genes, Helminth*
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Genes, Insect
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Genomics
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Insulin / metabolism
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Longevity / genetics
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Mutation
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Promoter Regions, Genetic
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RNA Interference
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Receptor, Insulin / genetics
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Receptor, Insulin / metabolism
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Signal Transduction
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Transcription Factors / genetics*
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Transcription Factors / physiology*
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Up-Regulation
Substances
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Caenorhabditis elegans Proteins
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Forkhead Transcription Factors
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Insulin
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Transcription Factors
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daf-16 protein, C elegans
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DAF-2 protein, C elegans
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Receptor, Insulin