Simple Nutrients Bypass the Requirement for HLH-30 in Coupling Lysosomal Nutrient Sensing to Survival.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA520897 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8528160.fastq.gz | Fastqsanger.gz | |||
| SRR8528170.fastq.gz | Fastqsanger.gz | |||
| SRR8528180.fastq.gz | Fastqsanger.gz | |||
| SRR8528161.fastq.gz | Fastqsanger.gz | |||
| SRR8528171.fastq.gz | Fastqsanger.gz |
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Project description:In this study, we subjected worms deficient in HLH-30, a master regulator of lysosome biogenesis, to starvation followed by refeding various food sources and analyzed their transcriptional profiles.
2019-05-14 | GSE126061 | GEO
Project description:Lysosomes are ubiquitous acidified organelles that degrade intracellular and extracellular material trafficked via multiple pathways. Lysosomes also sense cellular nutrient levels to regulate target of rapamycin (TOR) kinase, a signaling enzyme that drives growth and suppresses activity of the MiT/TFE family of transcription factors that control biogenesis of lysosomes. In this study, we subjected worms lacking basic helix-loop-helix transcription factor 30 (hlh-30), the Caenorhabditis elegans MiT/TFE ortholog, to starvation followed by refeeding to understand how this pathway regulates survival with variable nutrient supply. Loss of HLH-30 markedly impaired survival in starved larval worms and recovery upon refeeding bacteria. Remarkably, provision of simple nutrients in a completely defined medium (C. elegans maintenance medium [CeMM]), specifically glucose and linoleic acid, restored lysosomal acidification, TOR activation, and survival with refeeding despite the absence of HLH-30. Worms deficient in lysosomal lipase 2 (lipl-2), a lysosomal enzyme that is transcriptionally up-regulated in starvation in an HLH-30-dependent manner, also demonstrated increased mortality with starvation-refeeding that was partially rescued with glucose, suggesting a critical role for LIPL-2 in lipid metabolism under starvation. CeMM induced transcription of vacuolar proton pump subunits in hlh-30 mutant worms, and knockdown of vacuolar H+-ATPase 12 (vha-12) and its upstream regulator, nuclear hormone receptor 31 (nhr-31), abolished the rescue with CeMM. Loss of Ras-related GTP binding protein C homolog 1 RAGC-1, the ortholog for mammalian RagC/D GTPases, conferred starvation-refeeding lethality, and RAGC-1 overexpression was sufficient to rescue starved hlh-30 mutant worms, demonstrating a critical need for TOR activation with refeeding. These results show that HLH-30 activation is critical for sustaining survival during starvation-refeeding stress via regulating TOR. Glucose and linoleic acid bypass the requirement for HLH-30 in coupling lysosome nutrient sensing to survival.
| S-EPMC6516633 | biostudies-literature
Project description:Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly-discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans. However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. We demonstrated that G3PP (PGPH-2) overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and is an attractive target for age-related metabolic disorders linked to excess nutrients. This transcriptomics analysis was designed to determine genes that are differentially regulated in pgph-2 oe animals in comparison to wild-type animals on normal and excess glucose conditions. To determine the role of HLH-30 in the regulation of gene expression, we also used pgph-2 oe; hlh-30 and hlh-30 mutant animals and found a signature mediated by pgph-2 oe and HLH-30-dependent.
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Project description:In Caenorhabditis elegans, the six proteins that make up the REF-1 family are HES homologs that act in both Notch dependent and Notch-independent pathways to regulate embryonic events. To further our understanding of how the REF-1 family works to coordinate post-embryonic cellular events, we performed transcriptome analysis of HLH-25 and HLH-29 mutant strains. Gene expression microarray, including probe preparation, hybridization, fluidics run and chip scan, was performed by Georgia State University DNA/Protein Core Facility. Global gene expression in synchronized young adult populations of VC1220 (hlh-25 mutant) and tm284 (hlh-29 mutant) animals were compared to expression in N2 (wild-type) animals using GeneChip C. elegans Genome Array (Affymetrix). Data collection was carried out using GCOS 1.4 software (Affymetrix). Probe intensity values were normalized to a target value of 500 with normalization factor equal to 1. Data analysis was performed using GeneSpring GX 11 Software (Aglient, Palo Alto,CA).
2016-07-03 | E-GEOD-65417 | biostudies-arrayexpress
Project description:Purpose: Comparing the transcriptome of wild-type(N2), hlh-11 knock-out and hlh-11 over-expression worms to identify genes with differential expression. Methods: For each condition, two replicates were examined. For each sample, approximately 2,000 synchronized young adult worms were collected and resuspended in TRIzon Reagent (CW0580, CWBIO). Total RNA was isolated by chloroform extraction, followed by isopropanol precipitation. Sequencing was performed using HiSeq2500. The clean reads were aligned to WBcel235 genomes with TopHat2. Gene differential expression was analyzed using DEseq2. A threshold of p < 0.05 was set to determine differentially expressed genes. Induction (KO_up or OE_up) or suppression (KO_down or OE_down) of genes were obtained through comparing gene expressions in hlh-11 KO or OE worms to wild-type N2. Results: >86% reads were uniquely mapped. 2637 genes were significantly up regulated and 2845 genes were significantly down regulated in hlh-11 knock-out worms compared to wild-type. 107 genes were significantly up regulated and 237 genes were significantly down regulated in hlh-11 over-expression worms compared to wild-type. Conclusions: This study revealed the genes transcriptionally regulated by hlh-11.
2019-11-23 | GSE140866 | GEO
Project description:In Caenorhabditis elegans, the six proteins that make up the REF-1 family are HES homologs that act in both Notch dependent and Notch-independent pathways to regulate embryonic events. To further our understanding of how the REF-1 family works to coordinate post-embryonic cellular events, we performed transcriptome analysis of HLH-25 and HLH-29 mutant strains.
2016-01-01 | GSE65417 | GEO
Project description:To investigate the structure of the bodywall muscle differentiation network, we sought to both identify what role HLH-1 binding has in this regulation. We mapped the relationship between the regulatory targets and HLH-1 binding, as measured by ChIP-seq in animals enriched for bodywall muscle tissue through RNAi feeding. While regulatory targets are enriched for HLH-1 binding, the majority of HLH-1 binding actually occurs away from genes that are affected by hlh-1 loss of function. Nevertheless, HLH-1 binding is associated with both the expected E-box and, near genes belonging to specific regulatory subgroups, novel motifs that may serve as binding sites for cooperative transcription factors. HLH-1 binding genome-wide in the early embryo of C. elegans
2012-06-21 | E-GEOD-28561 | biostudies-arrayexpress
Project description:To investigate the structure of the bodywall muscle differentiation network, we sought to both identify what role HLH-1 binding has in this regulation. We mapped the relationship between the regulatory targets and HLH-1 binding, as measured by ChIP-seq in animals enriched for bodywall muscle tissue through RNAi feeding. While regulatory targets are enriched for HLH-1 binding, the majority of HLH-1 binding actually occurs away from genes that are affected by hlh-1 loss of function. Nevertheless, HLH-1 binding is associated with both the expected E-box and, near genes belonging to specific regulatory subgroups, novel motifs that may serve as binding sites for cooperative transcription factors.
2012-06-22 | GSE28561 | GEO
Project description:The hlh-30 gene encodes a C. elegans basic-helix-loop-helix (bHLH) transcription factor; We compared RNA from wild type worms and worms mutant for the hlh-30 gene to identify putative target genes of the HLH-30 transcription factor. Experiment Overall Design: Total RNA from three biological replicates were isolated from embryos, L1 larvae, and L2 larvae from both wild type and hlh-30(tm1978) mutant worms
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Project description:modENCODE_submission_2431 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: OP64(made_by : R. Waterston 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 HLH-1::EGFP fusion protein is expressed in the correct hlh-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the HLH-1 transcription factor. tags : GFP::3xFlag mutagen : Bombard outcross : 3 genotype : unc-119(ed3) III; wgIs64 [unc-119(+) hlh-1::TY1::EGFP::3xFLAG] official name : OP64 ); Developmental Stage: embryo; Genotype: unc-119(ed3) III; wgIs64 [unc-119(+) hlh-1::TY1::EGFP::3xFLAG]; Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage embryo; Target gene hlh-1; Strain OP64(made_by : R. Waterston 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 HLH-1::EGFP fusion protein is expressed in the correct hlh-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the HLH-1 transcription factor. tags : GFP::3xFlag mutagen : Bombard outcross : 3 genotype : unc-119(ed3) III; wgIs64 [unc-119(+) hlh-1::TY1::EGFP::3xFLAG] official name : OP64 ); temp (temperature) 20 degree celsius Series_type: CHIP-seq
2011-02-18 | E-GEOD-25784 | biostudies-arrayexpress