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Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin
Wendy B Iser1, Mark A Wilson, William H Wood
1Invertebrate Molecular Genetics Unit, Laboratory of Neurosciences, Research Resources Branch, NIA Intramural Research Program, NIH Biomedical Research Center, Baltimore, Maryland, United States of America.
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.
Insights
Insulin/IGF-I-like signaling (IIS) regulates cell functions. This study identifies new non-autonomous IIS targets in C. elegans, revealing a role for hsf-1 in mediating these effects.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Insulin/IGF-I-like signaling (IIS) governs cell-autonomous functions like growth and metabolism.
- Non-autonomous IIS functions, crucial for processes like C. elegans dauer morphogenesis, have poorly understood targets.
Purpose of the Study:
- To identify non-autonomous targets of C. elegans IIS using genomic and genetic methods.
- To investigate the role of specific genes, such as cyp-35B1, in IIS pathways.
Main Methods:
- Transcriptional microarrays to identify IIS-regulated genes in specific tissues (intestine, neurons).
- Tissue-restricted IIS manipulation to analyze gene expression changes.
- Genetic analysis of gene promoters, including DAF-16 and HSF-1 binding sites.
Main Results:
- IIS differentially regulates stress response genes, including hsp-16, in a tissue-specific manner.
- cyp-35B1/dod-13, a cytochrome P450 gene, is identified as a non-autonomous IIS target.
- DAF-16 and HSF-1 are direct regulators of the cyp-35B1 promoter.
Conclusions:
- hsf-1 is proposed to be involved in mediating the non-autonomous functions of age-1 in C. elegans.
- Understanding these IIS targets provides insights into developmental and stress response pathways.
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