title: Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.
abstract: Insulin/IGF-I-like signaling (IIS) has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.
authors.affiliation: Invertebrate Molecular Genetics Unit, Laboratory of Neurosciences, Research Resources Branch, NIA Intramural Research Program, NIH Biomedical Research Center, Baltimore, Maryland, United States of America.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Iser
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wilson
authors.forename: William H
authors.initials: WH
authors.lastname: Wood
authors.forename: Kevin
authors.initials: K
authors.lastname: Becker
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Wolkow
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007814:Larva; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D011972:Receptor, Insulin / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans; D003577:Cytochrome P-450 Enzyme System; D019869:Phosphatidylinositol 3-Kinases; C100662:AGE-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin