Expression data from CtBP knockdown MCF-7 cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36529 | GEO | 2013/03/20
SECONDARY ACCESSION(S): PRJNA155577
REPOSITORIES: GEO
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Project description:CtBP is a global co-repressor by serving as transcriptional factor in multiple pathways. CtBP functioned as transcriptional factor by recruiting other cofactors such as G9a, HDAC1 and PcG proteins. CtBP is found to be over enriched in several type of tumor samples. To dipict the role of CtBP in globally regulating gene expression, we applied gene microarray technology to find out what subgroups of genes are mainly affected. 6 MCF-7 cell samples, 3 with CtBP knockdown and 3 with control knock down.
2013-03-20 | E-GEOD-36529 | biostudies-arrayexpress
Project description:CtBP is a global co-repressor by serving as transcriptional factor in multiple pathways. CtBP functioned as transcriptional factor by recruiting other cofactors such as G9a, HDAC1 and PcG proteins. CtBP is found to be over enriched in several type of tumor samples. To dipict the role of CtBP in globally regulating gene expression, we applied ChIP-seq technology to find out the binding profile of CtBP in breast cancer cell line MCF-7. Our data suggest CtBP plays a global regulatory role in DNA damage repair, tumor initiation, and EMT process. Examine CtBP binding in MCF-7 cells
2013-03-20 | E-GEOD-36546 | biostudies-arrayexpress
Project description:CtBP is a global co-repressor by serving as transcriptional factor in multiple pathways. CtBP functioned as transcriptional factor by recruiting other cofactors such as G9a, HDAC1 and PcG proteins. CtBP is found to be over enriched in several type of tumor samples. To dipict the role of CtBP in globally regulating gene expression, we applied ChIP-seq technology to find out the binding profile of CtBP in breast cancer cell line MCF-7. Our data suggest CtBP plays a global regulatory role in DNA damage repair, tumor initiation, and EMT process.
2013-03-20 | GSE36546 | GEO
Project description:Purpose: The goals of this study are to find out CtBP and PcG coregulated targets through transcriptome profiling (RNA-seq). Methods: Kc cell mRNA profiles of 7-day Ctrl and CtBP and ph-p+E(z) RNAi were generated by deep sequencing, in triplicate, using Illumina HiSeqTM 2000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: hyper-geometric test and the Benjamini Hochberg FDR correction method and TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the drosophila genome (build dm6) and identified 11,282 transcripts in the 9 samples, among which 381 PcG targets were selected for further analysis. Hierarchical clustering of differentially expressed genes divided these targets into three groups named CtBP co-activated genes,CtBP unaffected genes and CtBP co-repressed genes respectivly. RNA-seq data confirmed CtBP co-activated genes contain 22 known homeobox genes, and 4 of these were validated with qRT–PCR. These results suggest that CtBP is selectively required for the activation of PcG-repressed genes, especially the homeobox transcription factors including Hox genes.Conclusions: Our study represents the first detailed analysis of CtBP and PcG coregulated targets.
2022-05-17 | GSE88807 | GEO
Project description:Branching from conduits is a defining feature of the gas delivery systems of invertebrates (tracheae built from epithelial cells) and vertebrates (vasculature lined by endothelial cells). Here, we show that the vertebrate transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for sprouting of primary human endothelial cells and for the normal development of the Danio rerio embryo blood circulatory system. Tel controls endothelial sprouting via binding to the generic co-repressor C-terminal binding protein (CtBP). In endothelial cells, the Tel:CtBP complex temporally restricts a VEGF-mediated pulse of dll4 expression and consequently integrates VEGFR intracellular signaling and intercellular Notch-Dll4 signaling. It further refines branching by regulating expression of other factors that constrain angiogenesis such as sprouty family members and ve-cadherin. Thus, the Tel:CtBP complex moderates the balance between positive and antagonistic angiogenesis cues and thereby conditions endothelial cells for angiogenesis. Since the activity of CtBP is attuned to intracellular NADH levels, our results raise the possibility that Tel-mediated sprouting could be sensitized to the metabolic status of the tissue. Tel control of branching appears to be evolutionarily conserved since Yan, the invertebrate orthologue of Tel, is similarly required for branching morphogenesis of the invertebrate tracheae. Collectively, our work suggests that Tel is a central regulator of angiogenesis and highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis. 2 independent screens were performed testing effects of knockdown of Tel or CtBP (screen 1) or effects of VEGF-A (screen 2) on Human Umbilical Vein Endothelial Cells (HUVECs). For screen 1 we tested 3 different conditions. We established stable HUVEC cell lines which were either infected with control lentivirus (Mock), or lentivirus expressing short hairpin RNA constructs for the specific knockdown of Tel(Teli) or CtBP2 (CtBP2i). Expression in the Teli and CtBP2i cell lines was compared to expression in the Mock cell line for screen 1. For screen 2 we tested 2 conditions. We exposed HUVECs to VEGF (50ng/mL) for 30 minutes (samplename: VEGF30) and compared the transcriptome of these cells to untreated HUVECs (VEGF0). For each condition 2 independent repeats were analyzed and expression of genes was averaged for each repeat. HUVECs were grown under standard conditions (37degrees Celsius, 5% CO2) in EGM2 medium (Lonza).
2010-09-09 | E-GEOD-19335 | biostudies-arrayexpress
Project description:Branching from conduits is a defining feature of the gas delivery systems of invertebrates (tracheae built from epithelial cells) and vertebrates (vasculature lined by endothelial cells). Here, we show that the vertebrate transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for sprouting of primary human endothelial cells and for the normal development of the Danio rerio embryo blood circulatory system. Tel controls endothelial sprouting via binding to the generic co-repressor C-terminal binding protein (CtBP). In endothelial cells, the Tel:CtBP complex temporally restricts a VEGF-mediated pulse of dll4 expression and consequently integrates VEGFR intracellular signaling and intercellular Notch-Dll4 signaling. It further refines branching by regulating expression of other factors that constrain angiogenesis such as sprouty family members and ve-cadherin. Thus, the Tel:CtBP complex moderates the balance between positive and antagonistic angiogenesis cues and thereby conditions endothelial cells for angiogenesis. Since the activity of CtBP is attuned to intracellular NADH levels, our results raise the possibility that Tel-mediated sprouting could be sensitized to the metabolic status of the tissue. Tel control of branching appears to be evolutionarily conserved since Yan, the invertebrate orthologue of Tel, is similarly required for branching morphogenesis of the invertebrate tracheae. Collectively, our work suggests that Tel is a central regulator of angiogenesis and highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis.
2010-09-09 | GSE19335 | GEO
Project description:Regulation of gene expression by the CtBP family of NADH-sensitive transcriptional regulators, in MCF7 cells under normoxia and hypoxia. To determine the effect of CtBP knockdown on gene expression in MCF7 we transfected cells with an siRNA (5′-GGGAGGACCUGGAGAAGUUdTdT-3′/3′-dTdTCCCUCCUGGACCUCUUCAA-5′, obtained from Ambion) targetting both CtBP1 and CtBP2 (versus control siRNA). After 48 hours cells were either transferred to a hypoxic chamber (1% oxygen), or maintained in normoxia, for 18 hours.
2021-02-01 | GSE111259 | GEO
Project description:In this study, we report that ZNF516 functions as a transcription repressor. We showed that ZNF516 is physically associated with the CtBP/LSD1/CoREST corepressor complex and transcriptionally represses the expression of a collection of genes including EGFR that are critically involved in cell proliferation and motility. We demonstrated that the ZNF516 inhibits the proliferation and invasive potential of breast cancer cells in vitro and suppresses breast cancer growth and metastasis in vivo. We explored the clinical significance of the ZNF516-CtBP/LSD1/CoREST-EGFR axis in breast carcinomas.
2017-05-01 | GSE97962 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal of human cancers underscoring the need to identify new therapeutic vulnerabilities. Previously, we reported high expression of transcriptional co-regulators C-terminal binding proteins (CtBP) 1 and 2 in human PDAC, however their precise role in PDAC formation or progression remains unclear. Here, we have studied PDAC tumor dependency on CtBPs for growth and metastasis using an orthotopic syngeneic pancreatic tumor mouse model. CRISPR-based homozygous deletion of Ctbp2 dramatically decreased PDAC tumor growth, drastically reduced metastatic potential, and significantly prolonged survival. Interrogating differential gene expression of the orthotopic PDAC tumors from CtBP2 WT vs. CtBP2 KO cohorts, we identified significant downregulation of the EGFR-superfamily receptor ErbB3 in CtBP2 KO tumors, and further determined that CtBP regulates expression of both the ErbB2 and 3 EGFR superfamily genes in PDAC cells. We therefore hypothesized that CtBP regulation of physiologic ErbB2/3 signaling contributes, in part, to PDAC growth and metastasis. Indeed, we observed that CtBP2 KO cells exhibited severely attenuated activation of phospho-Akt after neuregulin stimulation of ErbB2/3, and we demonstrate that human PDAC cells also show CtBP dependence of ErbB2/3 expression. Our results suggest that a subset of PDAC tumors is dependent on physiologic ErbB2/3 signaling and could be targeted by pharmacologic inhibitors of ErbB2 and/or ErbB3. Providing proof of concept, the ErbB2-targeted multikinase inhibitor lapatinib, but not the ErbB1/EGFR targeted agent erlotinib, effectively killed ErbB3 expressing PDAC cells, while CtBP2 KO cells where ErbB3 expression was extinguished, were resistant to lapatinib. Taken together, our data suggests that ErBb2/3 targeted therapeutics can effectively target a critical PDAC dependency on physiologic ErbB2/3 signaling which is the result of CtBP’s oncogenic transcriptional program that drives PDAC tumor progression.
2023-11-10 | GSE228625 | GEO
Project description:ctbp-1 mutant C. elegans display a number of late-onset defects in their AIA neurons including (so far only a few identified) changes in their transcriptional profile. We sought to better characterize the gene expression changes occuring in these neurons by conducting a single, exploratory single cell RNA-seq experiment comparing wild-type and ctbp-1(lf) mutant gene expression profiles. Our main focus was on changes occurring specifically in the AIA neurons, though we decided to sequence the whole of the C. elegans nervous system so as to have to possibility of analyzing data detailing changes in other cell types should we so choose
2022-01-10 | GSE179484 | GEO