Global proteomic- and transcriptomic analyses of starvation responses reveal a central role for lipoprotein metabolism in acute starvation survival in C. elegans
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE98919 | GEO | 2017/07/01
SECONDARY ACCESSION(S): PRJNA386884
REPOSITORIES: GEO
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Project description:Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we unveil that bacterial membrane pore-forming toxin (PFT) induces autophagy through an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.
2016-11-01 | GSE78878 | GEO
Project description:modENCODE_submission_4807 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: OP433(official name : OP433 genotype : unc-119(ed3) III; wgIs433(hlh-30::TY1 EGFP FLAG; unc-119(+)) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology and Genetics in Dresden description : using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The HLH-30::EGFP fusion protein is expressed in the correct hlh-30 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the HLH-30 transcription factor. made_by : Unknown ); Developmental Stage: Late Embryo; Genotype: unc-119(ed3) III; wgIs433(hlh-30::TY1 EGFP FLAG; unc-119(+)); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage Late Embryo; Target gene hlh-30; Strain OP433(official name : OP433 genotype : unc-119(ed3) III; wgIs433(hlh-30::TY1 EGFP FLAG; unc-119(+)) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology and Genetics in Dresden description : using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The HLH-30::EGFP fusion protein is expressed in the correct hlh-30 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the HLH-30 transcription factor. made_by : Unknown ); temp (temperature) 20 degree celsius
2013-07-11 | E-GEOD-48752 | biostudies-arrayexpress
Project description:modENCODE_submission_4806 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: OP433(official name : OP433 genotype : unc-119(ed3) III; wgIs433(hlh-30::TY1 EGFP FLAG; unc-119(+)) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology and Genetics in Dresden description : using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The HLH-30::EGFP fusion protein is expressed in the correct hlh-30 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the HLH-30 transcription factor. made_by : Unknown ); Developmental Stage: L4; Genotype: unc-119(ed3) III; wgIs433(hlh-30::TY1 EGFP FLAG; unc-119(+)); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L4; Target gene hlh-30; Strain OP433(official name : OP433 genotype : unc-119(ed3) III; wgIs433(hlh-30::TY1 EGFP FLAG; unc-119(+)) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology and Genetics in Dresden description : using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The HLH-30::EGFP fusion protein is expressed in the correct hlh-30 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the HLH-30 transcription factor. made_by : Unknown ); temp (temperature) 20 degree celsius
2013-07-11 | E-GEOD-48751 | biostudies-arrayexpress
Project description:Accumulating evidence has demonstrated the presence of inter-tissue communication regulating systemic aging, but the underlying molecular network has not been fully explored. We and others previously showed that two basic helix-loop-helix transcription factors, MML-1 and HLH-30, are required for lifespan extension in several longevity paradigms, including germline-less Caenorhabditis elegans. However, it is unknown what tissues these factors target to promote longevity. Here, using tissue-specific knockdown experiments, we found that MML-1 and its heterodimer partners MXL-2 and HLH-30 act primarily in neurons to extend longevity in germline-less animals. Neuronal functions of MML-1/MXL-2 and HLH-30 are also essential to prevent aging in non-neuronal tissues, including muscle and the intestine. Interestingly, however, both the temporal requirement and the downstream function of MML-1 in neurons were distinct from those of HLH-30. MML-1 was active early, while HLH-30 functioned later in life to sustain longevity in germline-less animals. Moreover, neuronal RNA interference (RNAi)-based transcriptome analysis revealed that the glutamate transporter GLT-5 is a novel downstream target of MML-1 but not HLH-30. Furthermore, the MML-1–GTL-5 axis in neurons is critical to prevent an age-dependent collapse of proteostasis and increased oxidative stress through autophagy and peroxidase MLT-7, respectively, in long-lived animals. Collectively, our study revealed that systemic aging is regulated by a novel molecular network involving neuronal MML-1 function in both neural and peripheral tissues.
2023-09-18 | GSE234430 | GEO
Project description:Accumulating evidence has demonstrated the presence of inter-tissue communication regulating systemic aging, but the underlying molecular network has not been fully explored. We and others previously showed that two basic helix-loop-helix transcription factors, MML-1 and HLH-30, are required for lifespan extension in several longevity paradigms, including germline-less Caenorhabditis elegans. However, it is unknown what tissues these factors target to promote longevity. Here, using tissue-specific knockdown experiments, we found that MML-1 and its heterodimer partners MXL-2 and HLH-30 act primarily in neurons to extend longevity in germline-less animals. Neuronal functions of MML-1/MXL-2 and HLH-30 are also essential to prevent aging in non-neuronal tissues, including muscle and the intestine. Interestingly, however, both the temporal requirement and the downstream function of MML-1 in neurons were distinct from those of HLH-30. MML-1 was active early, while HLH-30 functioned later in life to sustain longevity in germline-less animals. Moreover, neuronal RNA interference (RNAi)-based transcriptome analysis revealed that the glutamate transporter GLT-5 is a novel downstream target of MML-1 but not HLH-30. Furthermore, the MML-1–GTL-5 axis in neurons is critical to prevent an age-dependent collapse of proteostasis and increased oxidative stress through autophagy and peroxidase MLT-7, respectively, in long-lived animals. Collectively, our study revealed that systemic aging is regulated by a novel molecular network involving neuronal MML-1 function in both neural and peripheral tissues.
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2024-01-26 | PXD043101 | Pride
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2019-05-14 | GSE126061 | GEO
Project description:All animals have evolved the ability to survive nutrient deprivation, and nutrient signaling pathways are conserved modulators of health and disease. In C. elegans, late-larval starvation provokes adult reproductive diapause (ARD), a long-lived quiescent state that enables animals to survive months without food, yet underlying molecular mechanisms remain unknown. Here, we show that ARD is distinct from other forms of diapause, and shows surprisingly little requirement for canonical longevity pathways, autophagy and fat metabolism. Instead ARD depends dramatically on HLH-30/TFEB transcription factor to promote morphologic and metabolic remodeling involved in ARD entry, survival, and recovery, suggesting it is a master regulator of reproductive quiescence. TFEB transcriptome and genetic analyses reveal that Max-like HLH factors, mTOR, AMP-kinase, protein synthesis, and mitochondrial fusion are target processes that promote ARD longevity. Evidently reproductive quiescence rewires metabolism in unique ways to ensure long-term survival, and could illuminate similar mechanisms acting in latent tumorigenesis, and long-term fasting.
2020-03-30 | GSE126632 | GEO