DAF-16 target genes that control C. elegans life-span and metabolism.
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.
Lee
Siu Sylvia
SS
Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, 50 Blossom Street, Boston, MA 02114, USA.
Kennedy
Scott
S
Tolonen
Andrew C
AC
Ruvkun
Gary
G
D000818:Animals; D001665:Binding Sites; D002107:Caenorhabditis / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D019295:Computational Biology; D017124:Conserved Sequence; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D017344:Genes, Insect; D023281:Genomics; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D015854:Up-Regulation
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin