title: Direct and indirect gene regulation by a life-extending FOXO protein in C. elegans: roles for GATA factors and lipid gene regulators.
abstract: In long-lived C. elegans insulin/IGF-1 pathway mutants, the life-extending FOXO transcription factor DAF-16 is present throughout the animal, but we find that its activity in a single tissue can delay the aging of other tissues and extend the animal's life span. To better understand the topography of DAF-16 action among the tissues, we analyzed a collection of DAF-16-regulated genes. DAF-16 regulated most of these genes in a cell-autonomous fashion, often using tissue-specific GATA factors to direct their expression to specific tissues. DAF-16 could also act cell nonautonomously to influence gene expression. DAF-16 affected gene expression in other cells, at least in part, via the lipid-gene regulator MDT-15. DAF-16, and probably MDT-15, could act cell nonautonomously in the endoderm to ameliorate the paralysis caused by expressing Alzheimer's Aβ protein in muscles. These findings suggest that MDT-15-dependent intercellular signals, possibly lipid signals, can help to coordinate tissue physiology, enhance proteostasis, and extend life in response to DAF-16/FOXO activity.
authors: Department of Biochemistry and Biophysics, Mission Bay Genentech Hall, 600 16th Street, Room S312D, University of California, San Francisco, San Francisco, CA 94158-2517, USA.
authors: Peichuan
authors: P
authors: Zhang
authors: Meredith
authors: M
authors: Judy
authors: Seung-Jae
authors: SJ
authors: Lee
authors: Cynthia
authors: C
authors: Kenyon
mesh_terms: D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004707:Endoderm / Q000378:metabolism; D051858:Forkhead Transcription Factors; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008136:Longevity; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D050980:GATA Transcription Factors; C571065:MDT-15 protein, C elegans; D034741:RNA, Small Interfering; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin