Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1019228 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26116068.fastq.gz | Fastqsanger.gz | |||
| SRR26116068_1.fastq.gz | Fastqsanger.gz | |||
| SRR26116068_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
Similar Datasets
Project description:We previously reported a pathogenic de novo W342 mutation in the transcriptional corepressor CtBP1 in four independent patients with neurodevelopmental disabilities. Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CtBP1 mutation. Within this cohort we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia and tooth enamel defects present in all patients. The W342 mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins. Unbiased proteomic analysis demonstrated reduced interaction of several chromatin modifying factors with the CtBP1 W342 mutant. Genome-wide transcriptome analysis in human glioblastoma cells lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes. Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls. Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts. Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes.
2019-05-09 | PXD012702 | Pride
Project description:We previously reported a pathogenic de novo W342 mutation in the transcriptional corepressor CtBP1 in four independent patients with neurodevelopmental disabilities. Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CtBP1 mutation. Within this cohort we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia and tooth enamel defects present in all patients. The W342 mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins. Unbiased proteomic analysis demonstrated reduced interaction of several chromatin modifying factors with the CtBP1 W342 mutant. Genome-wide transcriptome analysis in human glioblastoma cells lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes. Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls. Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts. Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes.
2019-02-08 | GSE126253 | GEO
Project description:A recurrent de novo mutation in the transcriptional corepressor CTBP1 is associated with neurodevelopmental disabilities in children (Beck et al., 2016; Beck et al., 2019; Sommerville et al., 2017). All reported patients harbor a single recurrent de novo heterozygous missense mutation (p.R342W) within the cofactor recruitment domain of CtBP1. To investigate the transcriptional activity of the pathogenic CTBP1 mutant allele in physiologically relevant human cell models, we generated induced pluripotent stem cells (iPSC) from the dermal fibroblasts derived from patients and normal donors. The transcriptional profiles of the iPSC-derived ‘early’ neurons were determined by RNA-sequencing. Comparison of the RNA-seq data of the neurons from patients and normal donors revealed down regulation of gene networks involved in neurodevelopment, synaptic adhesion and anti-viral (interferon) response. Consistent with the altered gene expression patterns, the patient-derived neurons exhibited morphological and electrophysiological abnormalities, and susceptibility to viral infection. Taken together, our studies using iPSC-derived neuron models provide novel insights into the pathological activities of the CTBP1 p.R342W allele.
2020-09-30 | GSE158754 | GEO
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. We identified androgen-regulated long non-coding RNA, CTBP1-AS, located in the antisese region of CTBP1 gene. CTBP1-AS activate AR signaling by epigenetically repress AR-associated cofactors such as CTBP1 by interactign with RNA-binding protein PSF and recruiting HDAC complex to the target promoters. In order investigated the PSF target genes, we performed ChIP-seq analysis of PSF binding sites in prostate cancer cell line, LNCaP cells. We identified androgen dependent PSF binding regions in prostate cancer cell genome. We observed PSF bindings around the promoters of androgen repressed genes such as CTBP1, p53 and SMAD3. ChIP-sequence analysis of PSF binding sites in prostate cancer cells
2014-01-01 | E-GEOD-45124 | biostudies-arrayexpress
Project description:Prostate cancer is the most common cancer in men and Androgen receptor (AR) downstream signalings promote prostate cancer cell proliferation. We identified androgen-regulated long non-coding RNA, CTBP1-AS, located in the antisese region of CTBP1 gene. CTBP1-AS activate AR signaling by epigenetically repress AR-associated cofactors such as CTBP1 by interactign with RNA-binding protein PSF and recruiting HDAC complex to the target promoters. In order to investigate the CTBP1-AS and PSF function in prostate cancer cells, we performed gene expression in AR-positive prostate cancer cell lines after siPSF or siCTBP1-AS treatment. We also treated cells with vehicle or androgen to analyzed the effects of CTBP1-AS and PSF on AR function. Observation of androgen dependent gene expression changes after treatmet with siRNAs targeting CTBP1-AS and PSF with microarray.
2014-01-01 | E-GEOD-44264 | biostudies-arrayexpress
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. We identified androgen-regulated long non-coding RNA, CTBP1-AS, located in the antisese region of CTBP1 gene. CTBP1-AS activate AR signaling by epigenetically repress AR-associated cofactors such as CTBP1 by interactign with RNA-binding protein PSF and recruiting HDAC complex to the target promoters. In order investigated the PSF target genes, we performed ChIP-seq analysis of PSF binding sites in prostate cancer cell line, LNCaP cells. We identified androgen dependent PSF binding regions in prostate cancer cell genome. We observed PSF bindings around the promoters of androgen repressed genes such as CTBP1, p53 and SMAD3.
2014-01-01 | GSE45124 | GEO
Project description:Prostate cancer (PCa) is the most common cancer among men. Metabolic syndrome (MeS) is associated with increased PCa aggressiveness and recurrence. We propose C-terminal binding protein 1 (CTBP1), a transcripcional co-repressor, as a molecular link between these two conditions. CTBP1 depletion decreased PCa growth in MeS mice. The aim of this study was to investigate the molecular mechanisms that explain the link between MeS and PCa mediated by CTBP1. We found that CTBP1 repressed several mRNAs and miRNAs including Chloride Channel Accessory 2 (CLCA2) in prostate xenografts developed in MeS animals. CTBP1 bound to CLCA2 promoter and repressed its transcription and promoter activity in PCa cell lines. Furthermore, we found that CTBP1 formed a repressor complex with ZEB1, EP300 and HDACs that modulates the CLCA2 promoter activity. CLCA2 promoted PCa cell adhesion inhibiting Epithelial-Mesenchymal Transition (EMT) and activating CTNNB1 together with epithelial markers (CDH1) induction, and mesenchymal markers (SNAI2 and TWIST1) repression. Moreover, CLCA2 depletion in PCa cells injected s.c. in MeS mice increased the Circulating Tumor Cells (CTCs) foci compared to control. A miRNA expression microarray from PCa xenografts developed in MeS mice, showed 21 miRNAs modulated by CtBP1 involved in angiogenesis, extracellular matrix organization, focal adhesion and adherents junctions, among others. We found that miR-196b-5p directly targets CLCA2 by cloning CLCA2 3'UTR and performing reporter assays. Altogether, we identified a new molecular mechanism for PCa and MeS link based on CLCA2 repression by CTBP1 and miR-196b-5p molecules that might act as key factors in the progression onset of this disease. We used microarrays to identified the miRNAs regulated by CtBP1 in a Metabolic Syndrome model
2019-09-21 | GSE104119 | GEO
Project description:Prostate cancer is the most common cancer in men and Androgen receptor (AR) downstream signalings promote prostate cancer cell proliferation. We identified androgen-regulated long non-coding RNA, CTBP1-AS, located in the antisese region of CTBP1 gene. CTBP1-AS activate AR signaling by epigenetically repress AR-associated cofactors such as CTBP1 by interactign with RNA-binding protein PSF and recruiting HDAC complex to the target promoters. In order to investigate the CTBP1-AS and PSF function in prostate cancer cells, we performed gene expression in AR-positive prostate cancer cell lines after siPSF or siCTBP1-AS treatment. We also treated cells with vehicle or androgen to analyzed the effects of CTBP1-AS and PSF on AR function.
2014-01-01 | GSE44264 | GEO
Project description:Novel Pathogenic ATM Mutation with Ataxia-Telangiectasia in a Chinese Family
| PRJNA1182062 | ENA