ArticlePLoS genetics2011
DAF-12 regulates a connected network of genes to ensure robust developmental decisions.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
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- A drug-like molecule engages nuclear hormone receptor DAF-12/FXR to regulate mitophagy and extend lifespan.Nature aging · 2023Article
- Transcriptional and spatiotemporal regulation of the dauer program.Transcription · 2023Review
- Optimizing health-span: advances in stem cell medicine and longevity research.Medical review (2021) · 2023Article
- Both entry to and exit from diapause arrest in Caenorhabditis elegans are regulated by a steroid hormone pathway.Development (Cambridge, England) · 2022Article
- The CHARGE syndrome ortholog CHD-7 regulates TGF-β pathways inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Gene regulatory network inference in long-livediScience · 2022Article
- The development of the dog heartworm is highly sensitive to sterols which activate the orthologue of the nuclear receptor DAF-12.Scientific reports · 2020Article
- The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by Destabilizing LIN-28.Developmental cell · 2019Article
- Dauer signalling pathway model for Haemonchus contortus.Parasites & vectors · 2019Article
- Cell-autonomous and non-autonomous roles ofAging · 2019Article
- RNAi-mediated knockdown of daf-12 in the model parasitic nematode Strongyloides ratti.PLoS pathogens · 2019Article
- Comparative bioinformatic analysis suggests that specific dauer-like signalling pathway components regulate Toxocara canis development and migration in the mammalian host.Parasites & vectors · 2019Article
- Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-PPAR research · 2019Article
- Nuclear receptors: emerging drug targets for parasitic diseases.The Journal of clinical investigation · 2017Review
- Regulation of Life Cycle Checkpoints and Developmental Activation of Infective Larvae in Strongyloides stercoralis by Dafachronic Acid.PLoS pathogens · 2016Article
- Serum α-klotho concentrations during preimplantation can predict aging or quality of human oocytes and clinical pregnancy rates.SpringerPlus · 2016Article
- dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.PLoS genetics · 2015Article
- Caenorhabditis elegans microRNAs of the let-7 family act in innate immune response circuits and confer robust developmental timing against pathogen stress.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development in unfavorable conditions, and the modulation of adult aging. Despite the biologic importance of DAF-12, target genes for this receptor are largely unknown. To identify DAF-12 targets, we performed chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays. We identified 1,175 genomic regions to be bound in vivo by DAF-12, and these regions are enriched in known DAF-12 binding motifs and act as DAF-12 response elements in transfected cells and in transgenic worms. The DAF-12 target genes near these binding sites include an extensive network of interconnected heterochronic and microRNA genes. We also identify the genes encoding components of the miRISC, which is required for the control of target genes by microRNA, as a target of DAF-12 regulation. During reproductive development, many of these target genes are misregulated in daf-12(0) mutants, but this only infrequently results in developmental phenotypes. In contrast, we and others have found that null daf-12 mutations enhance the phenotypes of many miRISC and heterochronic target genes. We also find that environmental fluctuations significantly strengthen the weak heterochronic phenotypes of null daf-12 alleles. During diapause, DAF-12 represses the expression of many heterochronic and miRISC target genes, and prior work has demonstrated that dauer formation can suppress the heterochronic phenotypes of many of these target genes in post-dauer development. Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions.
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Registered trials
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