RNA-seq from hypoxia pathway C. elegans mutants hif-1 (ia4) and vhl-1 (ok161)
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB71463 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR12383200_1.fastq.gz | Fastqsanger.gz | |||
| ERR12383200_2.fastq.gz | Fastqsanger.gz | |||
| ERR12383201_1.fastq.gz | Fastqsanger.gz | |||
| ERR12383201_2.fastq.gz | Fastqsanger.gz | |||
| ERR12383186_1.fastq.gz | Fastqsanger.gz |
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Project description:The extracellular matrix (ECM) is a pivotal three-dimensional network crucial for tissue organization, cellular communication, and fundamental cellular processes, where collagens are the major chemical entity in amount. Loss of pVHL is associated with the activation of hypoxia-inducible factor (HIF) signaling. Mutation of VHL-1 in the nematode Caenorhabditis elegans has been shown to increase lifespan and stress resistance. Interestingly, considering recent findings on the involvement of collagens in the regulation of lifespan, we also observed these worms to show defects in body morphology in a HIF-1 dependent manner. Here we investigate the impact of vhl-1 (ok161) and hif-1 (ia4) individually and combined over the transcriptome of adult C. elegans worms grown under basal (20°C) conditions, and pay close attention to how genes related to body morphology, such as genes coding for collagens, are regulated.
2026-06-30 | E-MTAB-13659 | biostudies-arrayexpress
Project description:The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated a subunits of hypoxia-inducible factor (HIF). Although studies of VHL defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways distinct from HIF. Here, we report on a genetic analysis of HIF dependent and independent effects of VHL inactivation by studying gene expression patterns in C. elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1 independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17 and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1 independent function of VHL-1 that is connected with extracellular matrix function.
2013-01-30 | E-SMDB-23 | biostudies-arrayexpress
Project description:Hypoxia inducible transcription factor HIF is the master regulator of hypoxia response in metazoans. The stability and activity of HIF are tightly regulated. In the model organism C. elegans, the homolog of HIF is HIF-1. The stability and activity of HIF-1 are negatively regulated by vhl-1, egl-9, rhy-1 and swan-1 when HIF-1 is stabilized by vhl-1 mutation. Here, we are using Affymetrix microarray to measure the immediate gene expression changes under short-term hypoxia treatment (2 hours of 0.5% oxygen treatment). We also want to understand whether the HIF-1 acvitity negative regulators function in common pathway(s) to regulate HIF-1 activity or not. We find that gene expression patterns in these HIF-1 activity negative regulator mutants are extraordinarily similar, which supports the model that they function in common pathway(s) to regulate HIF-1 activity.
2023-04-15 | GSE228851 | GEO
Project description:The goal of the study was to identify hypoxia-induced gene expression changes in C. elegans and to determine which of these responses to hypoxia were regulated by hif-1. Towards these aims, we analyzed mRNA expression patterns in synchronized populations of wild-type worms that were cultured in standard lab conditions (Snormoxia) or in hypoxia. We also assayed mRNA from two mutant strains: (i) animals carrying the strong loss-of-function mutation in hif-1 and (ii) C. elegans that carry a deletion in vhl-1 and express the HIF-1 protein at constitutively high levels. In the microarray experiments, 3 strains were assayed: wild type N2, hif-1 (ia04), and vhl-1 (ok161). Worms were incubated for 4 hours in 21% oxygen or 0.1% oxygen at 210C. Animals were quickly harvested in ice cold M9 buffer, and poly (A) RNA was isolated using established procedures. No more than 3 minutes elapsed between the removal of plates from the hypoxic chamber and the addition of Trizol. RNA was isolated from three independent experiments for each experimental condition (3 genotypes; normoxia vs hypoxia). mRNAs were hybridized to whole-genome microarrays which contained probes for 17,817 predicted genes (94% of the genome). Ch1 in the array reprents the data for the worms growed under hypoxia; and Ch2 in the array reprents the data for the worms growed under normoxia.
2005-06-20 | E-SMDB-3266 | biostudies-arrayexpress
Project description:Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.
2012-12-05 | E-GEOD-32299 | biostudies-arrayexpress
Project description:The response to insufficient oxygen, termed hypoxia, is orchestrated by the conserved master regulator Hypoxia-Inducible Factor-1 (HIF-1), which is hyperactive in many cancers. Here, we describe a HIF-1 independent hypoxia response pathway controlled by Caenorhabditis elegans Nuclear Hormone Receptor NHR-49, an orthologue of mammalian lipid metabolism regulator Peroxisome Proliferator-Activated Receptor alpha (PPARα). nhr-49 is required for worm survival in hypoxia and is synthetically lethal with hif-1 in this context, demonstrating independent activity. RNA-seq data show that nhr-49 regulates a set of hif-1 independent hypoxia responsive genes, including autophagy genes that promote hypoxia survival. We further identified the Nuclear Hormone Receptor nhr-67 as a negative regulator and the Homeodomain-interacting Protein Kinase hpk-1 as a positive regulator in the NHR-49 pathway. Together, our experiments describe an essential hypoxia response pathway controlled by nhr-49 that includes new upstream and downstream components and is as important as hif-1 dependent hypoxia adaptation.
2022-03-16 | GSE166788 | GEO
Project description:Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway. This SuperSeries is composed of the SubSeries listed below.
2012-12-05 | GSE32299 | GEO
Project description:Human renal cell carcinomas (RCC) have differential expression of HIF-1alpha and HIF-2alpha, depending on VHL genotype and other events. Here, we have divided a series of RCC samples for HIF-alpha expression and VHL genotype, in order to define differentially expressed genes Keywords: Patient Sample Study A total of 57 frozen RCC samples were stained for HIF-1alpha and HIF-2alpha, and genotyped for VHL. 5 VHL WT/HIF-negative, 8 VHL-deficient/HIF-1alpha+/HIF-2alpha+ and 8 VHL-deficient/HIF-2alpha+ tumors were selected for microarray
2008-12-27 | E-GEOD-11904 | biostudies-arrayexpress
Project description:We have generated two zebrafish lines carrying inactivating germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene ortholog vhl. Mutant embryos display a general systemic hypoxic response, including the upregulation of hypoxia-induced genes by 1 day post-fertilization and a severe hyperventilation and cardiophysiological response. vhl mutants develop polycythemia with concomitantly increased epo/epor mRNA levels and Epo signaling. In situ hybridizations reveal global up-regulation of both red and white hematopoietic lineages. Hematopoietic tissues are highly proliferative, with enlarged populations of c-myb+ HSCs and circulating erythroid precursors. Chemical activation of Hif-signaling recapitulated aspects of the vhl-/- phenotype. Furthermore, microarray expression analysis confirms the hypoxic response and hematopoietic phenotype observed in vhl-/- embryos. We conclude that Vhl participates in regulating hematopoiesis and erythroid differentiation. Injections with human VHLp30 and R200W mutant mRNA demonstrate functional conservation of VHL between mammals and zebrafish at the amino acid level, indicating that vhl mutants are a powerful new tool to study genotype-phenotype correlations in human disease. Zebrafish mutants are the first congenital embryonic viable systemic vertebrate animal model for VHL, representing the most accurate model for VHL-associated polycythemia to date. They will contribute to our understanding of hypoxic signaling, hematopoiesis and VHL-associated disease progression.
2009-03-01 | GSE14866 | GEO
Project description:The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated a subunits of hypoxia-inducible factor (HIF). Although studies of VHL defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways that are distinct from HIF. Here, we report on a genetic analysis of HIF dependent and independent effects of VHL inactivation by studying gene expression patterns in C. elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1 independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17 and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1 independent function of VHL-1 that is connected with extracellular matrix function. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Bishop T, Lau KW, Epstein AC, Kim SK, Jiang M, O'rourke D, Pugh CW, Gleadle JM, Taylor MS, Hodgkin J, Ratcliffe PJ, Genetic Analysis of Pathways Regulated by the von Hippel-Lindau Tumor Suppressor in Caenorhabditis elegans., Bishop T, et al. (2004) PLoS Biol 2(10):e289, 2004-10-01, http://biology.plosjournals.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.0020289 Computed
2005-07-20 | E-GEOD-2963 | biostudies-arrayexpress