Caenorhabditis elegans
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-40127
PROVIDER: PRJNA172868 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:NCoR and SMRT are two paralogous vertebrate proteins that function as corepressors with unliganded nuclear receptors. Although C. elegans has a large number of nuclear receptors, orthologues of the corepressors NCoR and SMRT have not unambiguously been identified in Drosophila or C. elegans. Here, we identify GEI-8 as the closest homologue of NCoR and SMRT in C. elegans and demonstrate that GEI-8 is expressed as at least two isoforms throughout development in multiple tissues, including neurons, muscle and intestinal cells. We demonstrate that a homozygous deletion within the gei-8 coding region, which is predicted to encode a truncated protein lacking the predicted NR domain, results in severe mutant phenotypes with developmental defects, slow movement and growth, arrested gonadogenesis and defects in cholinergic neurotransmission. Whole genome expression analysis by microarrays identified sets of de-regulated genes consistent with both the observed mutant phenotypes and a role of GEI-8 in regulating transcription. Interestingly, the upregulated transcripts included a predicted mitochondrial sulfide:quinine reductase encoded by Y9C9A.16. This locus also contains non-coding, 21-U RNAs of the piRNA. Inhibition of the expression of the region coding for 21-U RNAs leads to irregular gonadogenesis in the homozygous gei-8 mutants, but not in an otherwise wild-type background, suggesting that GEI-8 may function in concert with the 21-U RNAs to regulate gonadogenesis. Our results confirm that GEI-8 is the orthologue of the vertebrate NCoR/SMRT corepressors and demonstrate important roles for this putative transcriptional corepressor in development and neuronal function. Comparison of Mutant vs. WT control with three replications per treatment group
2013-08-11 | E-GEOD-40127 | biostudies-arrayexpress
Project description:NCoR and SMRT are two paralogous vertebrate proteins that function as corepressors with unliganded nuclear receptors. Although C. elegans has a large number of nuclear receptors, orthologues of the corepressors NCoR and SMRT have not unambiguously been identified in Drosophila or C. elegans. Here, we identify GEI-8 as the closest homologue of NCoR and SMRT in C. elegans and demonstrate that GEI-8 is expressed as at least two isoforms throughout development in multiple tissues, including neurons, muscle and intestinal cells. We demonstrate that a homozygous deletion within the gei-8 coding region, which is predicted to encode a truncated protein lacking the predicted NR domain, results in severe mutant phenotypes with developmental defects, slow movement and growth, arrested gonadogenesis and defects in cholinergic neurotransmission. Whole genome expression analysis by microarrays identified sets of de-regulated genes consistent with both the observed mutant phenotypes and a role of GEI-8 in regulating transcription. Interestingly, the upregulated transcripts included a predicted mitochondrial sulfide:quinine reductase encoded by Y9C9A.16. This locus also contains non-coding, 21-U RNAs of the piRNA. Inhibition of the expression of the region coding for 21-U RNAs leads to irregular gonadogenesis in the homozygous gei-8 mutants, but not in an otherwise wild-type background, suggesting that GEI-8 may function in concert with the 21-U RNAs to regulate gonadogenesis. Our results confirm that GEI-8 is the orthologue of the vertebrate NCoR/SMRT corepressors and demonstrate important roles for this putative transcriptional corepressor in development and neuronal function.
2013-08-11 | GSE40127 | GEO
Project description:GEI-8, a homologue of vertebrate nuclear receptor corepressor NCoR/SMRT, regulates development and neuronal functions in C. elegans.
2015-09-30 | E-GEOD-40127 | ExpressionAtlas
Project description:Here, we systemically investigated the GPS2 corepressor complex function on cyclooxygenase 1 (Ptgs1) in macrophage M2 activation. We found the inflammatory states changed the DNA topology structure along with the histone modification and the gene expression on Ptgs1 locus. GPS2 related NCOR/SMRT corepressor physically bound to Ptgs1 promoter and enhancer, and depletion of all corepressor subunits caused the basal overexpression of Ptgs1 along with the H3K27ac activation. The corepressor subunits display a conserved function on Ptgs1 expression in M2 activation and this regulation is dependent on STAT6 but not through the direct interaction. We find the GPS2 depletion interferences the DNA accessibility on Ptgs1 locus and promotes the enhancer-promoter interaction and the transcriptional process in M2 activation. We further find the GPS2 depletion caused the recruitments of KDM1A, which specifically demethylated the H3K9me2/3 on Ptgs1 locus. In summary, these findings suggest a new paradigm of the corepressor mediated common gene repression in M2 activation and indicate the potential function of the GPS2/NCOR/SMRT function in the tissue homeostasis and wound healing during Th2-mediated immune responses.
2022-12-14 | GSE184884 | GEO
Project description:We profiled gene expression in livers depleted of NCOR (nuclear receptor corepressor) along with wild-type livers as control.
2013-11-25 | GSE49387 | GEO
Project description:Nuclear receptor corepressor (NCOR) and HDAC3 in hypothalamus
| PRJNA357597 | ENA
Project description:We profiled gene expression in livers depleted of NCOR (nuclear receptor corepressor) along with wild-type livers as control. NCOR floxed mice were intravenously injected with adeno-associated virus (AAV) expressing Cre or GFP. Livers were harvested at 2-weeks post-injection at 5pm (ZT10). Total RNA was extracted and hybridized to Affymetrx Mouse Gene 2.0 array.
2013-11-25 | E-GEOD-49387 | biostudies-arrayexpress
Project description:Changing the somatic cell transcriptome to a pluripotent state using exogenous reprogramming factors needs transcriptional co-regulators that help activate or suppress gene expression and rewrite the epigenome. Here, we show that reprogramming-specific engagement of the NCoR/SMRT co-repressor complex at key pluripotency loci creates an epigenetic block to reprogramming. HDAC3 executes the repressive function of NCoR/SMRT in reprogramming by inducing histone deacetylation at these loci. Recruitment of NCoR/SMRT-HDAC3 to pluripotency genes is facilitated by all 4 Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) but mostly by c-MYC. Class IIa HDACs further potentiate this recruitment by interacting with both the reprogramming factors and NCoR/SMRT. Consequently, depleting NCoR/SMRT-HDAC3 function enables high efficiency of reprogramming, while elevating NCoR/SMRT-HDAC3 recruitment at pluripotency loci by over-expressing constitutively active class IIa HDACs derails it. Our findings thus uncover an unexpected epigenetic mechanism involving c-MYC, whose manipulation greatly enhances reprogramming efficiency.
2018-03-07 | GSE70738 | GEO
Project description:Changing the somatic cell transcriptome to a pluripotent state using exogenous reprogramming factors needs transcriptional co-regulators that help activate or suppress gene expression and rewrite the epigenome. Here, we show that reprogramming-specific engagement of the NCoR/SMRT co-repressor complex at key pluripotency loci creates an epigenetic block to reprogramming. HDAC3 executes the repressive function of NCoR/SMRT in reprogramming by inducing histone deacetylation at these loci. Recruitment of NCoR/SMRT-HDAC3 to pluripotency genes is facilitated by all 4 Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) but mostly by c-MYC. Class IIa HDACs further potentiate this recruitment by interacting with both the reprogramming factors and NCoR/SMRT. Consequently, depleting NCoR/SMRT-HDAC3 function enables high efficiency of reprogramming, while elevating NCoR/SMRT-HDAC3 recruitment at pluripotency loci by over-expressing constitutively active class IIa HDACs derails it. Our findings thus uncover an unexpected epigenetic mechanism involving c-MYC, whose manipulation greatly enhances reprogramming efficiency.
2018-03-07 | GSE70736 | GEO
Project description:Heme is the endogenous ligand for the constitutively repressive REV-ERB nuclear receptors, REV-ERBα (NR1D1) and REV-ERBβ (NR1D2), but how heme regulates REV-ERB activity remains unclear. While cellular studies indicate heme is required for the REV-ERBs to bind the corepressor NCoR and repress transcription, fluorescence-based biochemical assays and crystal structures suggest that heme displaces NCoR. Here, we found that heme artifactually influences detection of NCoR interaction in fluorescence-based assays. Using fluorescence-independent methods, including isothermal titration calorimetry, NMR spectroscopy, and XL-MS, we determined that heme remodels the thermodynamic profile of NCoR binding to REV-ERBβ ligand-binding domain (LBD) and directly increases LBD binding affinity for an NCoR interaction motif. We further report two crystal structures of REV-ERBβ LBD cobound to heme and NCoR peptides, which reveal the heme-dependent NCoR binding mode. By resolving previous contradictory biochemical, structural, and cellular studies, our findings should facilitate renewed progress toward understanding heme-dependent REV-ERB activity.
2021-02-24 | PXD021761 | Pride