The effect of CTBP dehydrogenase inhibitors MTOB and 4-Cl-HIPP in J774.1 cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1185200 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:C-terminal binding proteins (CTBPs) are conserved transcriptional repressors involved in cancer and inflammation. Uniquely amongst transcriptional coregulators, CTBPs possess a functional dehydrogenase domain. Since multiple malignancies display elevated CTBP levels, CTBP inhibitors targeting this dehydrogenase domain have been developed. While the importance of CTBPs dehydrogenase function for transcriptional regulation remains unclear, multiple studies have relied CTBP inhibitors such as MTOB and 4-Cl-HIPP. In vitro studies have confirmed binding of these compounds to CTBP’s active site, however evidence for specificity is currently lacking. To address this, we treated wildtype or Ctbp1, 2 double knockout J774.1 cells with MTOB or 4-Cl-HIPP and performed RNAseq. We observed that both inhibitors elicit distinct transcriptional changes indicating non-overlapping modes of action. Moreover, the majority of changes induced by either inhibitor are observed in knockout cells indicative of off-target effects. We hypothesize that those CTBP dehydrogenase inhibitors might lack specificity to CTBPs.
2025-02-25 | GSE281668 | GEO
Project description:Both TRIM28 and CtBP are important transcriptional repressors and always shown high expression in many types of cancers, in our current study, we found TRIM28 interacts with CtBP in breast cancer and normal cells. To elucidate the functions of interaction between TRIM28 and CtBP in breast cancer progression, we performed the RNAseq of knocking down TRIM28, CtBP and Ctrl(NC) genes in MCF-7 cell line.
2025-01-18 | GSE287092 | GEO
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:Effect of novel aldehyde dehydrogenase inhibitors. Before an experiment medium was replaced to medium without glucose with addition of labeled glucose on C13. Next, cells were treated with ALDH inhibitors 673 or 773 for 1, 4, or 8 hr (673&773-Jan26)
2017-06-19 | ST000774 | MetabolomicsWorkbench
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 gene microarray technology to find out what subgroups of genes are mainly affected.
2013-03-20 | GSE36529 | GEO
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: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: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