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Transcriptional profiling of Caenorhabditis elegans nematodes treated with L4440 (Empty Vector - EV) or grd-1 RNAi from L1 hatch, and collected at L3 of development.

ABSTRACT: Hedgehog morphogen GRD-1 regulates C. elegans growth and metabolism downstream of TOR complex 2. Both Hedgehog (Hh) signaling and target of rapamycin complex 2 (TORC2) are evolutionarily conserved pathways that regulate growth and metabolism. In C. elegans, loss of Hh morphogens often leads to developmental arrest, while loss of essential TORC2 component RICTOR (rict-1) causes delayed development, reduced brood, small size, increased fat, and shortened lifespan. Here we report that knockdown of Hh-related morphogen grd-1 causes developmental acceleration rather than arrest by speeding up molting transitions. Further, we show that RNAi to grd-1 not only suppresses the slow growth of rict-1 mutants, but also normalizes multiple abnormalities downstream of TORC2 including restoration of lifespan to near normal and partial rescue of low brood, small body size, and increased fat. Mechanistically, grd-1 slows growth downstream of TORC2 at least in part by increasing transcription of paraquat mediator 1 (PQM-1) target genes. Given the important role of TORC2 in governance of development, these data implicate grd-1 and pqm-1 as critical executors of organismal growth slowing in response to unfavorable growth conditions downstream of the nutrient sensor TORC2 in C. elegans.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE211807 | GEO | 2023/08/22

REPOSITORIES: GEO

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Project description:modENCODE_submission_2623 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP201(made_by : S Kim description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The PQM-1::EGFP fusion protein is expressed in the correct pqm-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the PQM-1 transcription factor. tags : GFP::3xFlag mutagen : Bombard outcross : 3 genotype : unc119(ed3);wgIs201(pqm-1::TY1 EGFP FLAG C;unc119) official name : OP201 ); Developmental Stage: L3; Genotype: unc119(ed3);wgIs201(pqm-1::TY1 EGFP FLAG C;unc119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L3; Target gene pqm-1; Strain OP201(made_by : S Kim description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The PQM-1::EGFP fusion protein is expressed in the correct pqm-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the PQM-1 transcription factor. tags : GFP::3xFlag mutagen : Bombard outcross : 3 genotype : unc119(ed3);wgIs201(pqm-1::TY1 EGFP FLAG C;unc119) official name : OP201 ); temp (temperature) 20 degree celsius Series_type: CHIP-seq

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Transcriptional profiling of Caenorhabditis elegans nematodes treated with L4440 (Empty Vector - EV) or grd-1 RNAi from L1 hatch, and collected at L3 of development.

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