Effect of depletion of vhl-1 on gene expression in young adult C. elegans
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE224016 | GEO | 2023/04/04
REPOSITORIES: GEO
Similar Datasets
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: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
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 Keywords: Logical Set
2005-07-20 | GSE2963 | 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:Gene expression is a major determinant of cell fate and physiology, yet it is notoriously difficult to characterize for the widely used model system C. elegans. By using a new method based on in vivo covalent modification of DNA by RNA polymerases, we determine genome-wide transcription patterns in single tissues of embryos or young adult animals. We show that the method is able to identify actively transcribed genes in tissues representing down to 0.2% of the somatic cells in adult animals. Additionally, this method can be fully performed in a single laboratory by using third generation sequencing methods (ONT).
2020-10-28 | GSE157416 | GEO
Project description:The nematode Caenorhabditis elegans exhibits rapid senescence that is promoted by the insulin/IGF-1 signaling (IIS) pathway via regulated processes that are poorly understood. IIS also promotes production of yolk for egg provisioning, which in post-reproductive animals continues, supported by destructive repurposing of intestinal biomass that contributes to senescence. Post-reproductive mothers vent this yolk which can be consumed by larvae and promotes their growth. This implies that later yolk production is not futile; instead vented yolk functions similarly to milk. Moreover, yolk venting is promoted by IIS. That this process is promoted by IIS provides new insights into how and why IIS shortens lifespan in C. elegans. Fully-fed d4 hermaphrodites were allowed to vent for 30 min, and vented proteins analysed against excretory/secretory products collected for L3 larvae as a negative control.
2022-02-17 | PXD025472 | Pride
Project description:We performed RNA interactome capture in wild type compared to vhl-1(ok161) loss-of-function worms. These data are combined with the proteome to distinguish changes in RBP abundance from differential binding events.
2020-01-08 | PXD014469 | Pride
Project description:Transcriptional profiling of adult C. elegans comparing daf-16(-); daf-2(-) animals with adult daf-2(-) animals. Two-condition experiment, daf-2 mutants treated with daf-16 RNAi vs. daf-2 mutants treated with empty vector RNAi. Biological replicates: 8 daf-2 mutants treated with daf-16 RNAi vs. daf-2 mutants treated with empty vector RNAi, independently grown and harvested. One replicate per array.
2010-05-16 | E-GEOD-18561 | biostudies-arrayexpress
Project description:Neuropeptides constitute a vast and functionally diverse family of neurochemical signaling molecules, and are widely involved in the regulation of various physiological processes. The nematode C. elegans is well-suited for the study of neuropeptide biochemistry and function, as neuropeptide biosynthesis enzymes are not essential for C. elegans viability. This permits the study of neuropeptide biosynthesis in mutants lacking certain neuropeptide-processing enzymes. Mass spectrometry has been used to study the effects of proprotein convertase and carboxypeptidase mutations on proteolytic processing of neuropeptide precursors and on the peptidome in C. elegans. However, the enzymes required for the last step in the production of many bioactive peptides – the carboxyterminal amidation reaction – have not been characterized in this manner. Here, we describe three genes that encode homologs of neuropeptide amidation enzymes in C. elegans and used tandem LC-MS to compare neuropeptides in wild-type animals with those in newly generated mutants for these putative amidation enzymes. We report that mutants lacking both a functional peptidylglycine α-hydroxylating monooxygenase (PHM) and a peptidylglycine α-amidating monooxygenase (PAM) had a severely altered neuropeptide profile and also a decreased number of offspring. Interestingly, single mutants of the amidation enzymes still expressed some fully processed amidated neuropeptides, indicating the existence of a redundant amidation mechanism in C. elegans. In summary, the key steps in neuropeptide-processing in C. elegans seem to be executed by redundant enzymes, and loss of these enzymes severely affects brood size, supporting the need of amidated peptides for C. elegans reproduction.
2018-03-12 | PXD008942 | Pride