Effect of expression of a PI3-Kinase Dp110 dominant-negative (Dp110-DN) trangene on gene expression in fly fat body
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PROVIDER: PRJNA531271 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression pattern in fat bodies of flies expressing (or not) a dominant-negative form of the PI3K Dp110 (UAS-Dp110-DN, D954A) driven from a constitutive fat body-specific driver (FB-GAL4).
2020-01-01 | GSE129430 | GEO
Project description:Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) is a late onset disorder, due to mutations in DNA methyltransferase type 1 (DNMT1). Yet our understanding of how these mutations in DNMT1 lead to the clinical phenotypes of ADCA-DN is still unclear. To address this, we used fibroblasts, induced pluripotent stem cells (iPSCs) and induced neurons (iNs) generated from patients with ADCA-DN and controls, to determine the underlining epigenomic changes. Here we show that the differential expression pattern and differential methylation spectrum between patients and controls were tissue-specific. Furthermore, methylation and gene expression changes were negatively correlated in iPSCs and iNs. In addition, we identified a group of genes associated with clinical phenotypes of ADCA-DN, including PDGFB and PRDM8 for cerebellar ataxia, psychosis and dementia, and NR2F1 for deafness and optic atrophy. We further showed that ZFP57, which is required to maintain gene imprinting through DNA methylation during early development, was hypomethylated in promoters and exhibited upregulated expression in patients with ADCA-DN in both iPSC and iNs. Our results provide insight into the molecular changes associated with ADCA-DN, with potential implications for genes associated with related phenotypes.
2022-02-20 | GSE126890 | GEO
Project description:Bulk MARS-seq analysis of gene expression in exocrine cells infected with Ad-PDX1, Ad-DN-REST or both. DN-REST activated endocrine genes, many of which exhibited a synergistic effect in coexpression with PDX1. PDX1 alone activated exocrine genes.
2020-03-25 | GSE128546 | GEO
Project description:RAS signalling through Phosphoinositide 3-kinase (PI3-Kinase) has been shown to have an essential role in tumour initiation and maintenance. RAS also regulates cell motility and tumor invasiveness, but the role of direct RAS binding to PI3-Kinase in this remains uncertain. Here, we provide evidence that disruption of RAS interaction with PI3-Kinase p110adecreases cell motility and prevents activation of Rac GTPase. Analysis of gene expression in cells lacking RAS interaction with p110areveals increased levels of the extracellular matrix glycoprotein Reelin and activation of its downstream pathway resulting in upregulation of E-Cadherin expression. Induction of the Reelin / E-Cadherin axis is also observed in Kras mutant lung tumours that are regressing due to blockade of RAS interaction with PI3-Kinase. Furthermore, loss of Reelin correlates with decreased survival of lung and breast cancer patients. Reelin thus plays a role in restraining RAS and PI3-kinase promotion of cell motility and potentially tumour metastasis.
2016-02-12 | GSE77843 | GEO
Project description:The homeostasis of both cornea and hair follicles depends on a constant supply of progeny cells produced by populations of keratin (K) 14-expressing stem cells localized in specific niches. To investigate the potential role of Co-factors of LIM domains (Clims) in such tissues, we generated transgenic mice expressing a dominant-negative Clim molecule (DN-Clim) under the control of the K14 promoter. As expected, the K14 promoter directed high level expression of the transgene to the basal cells of cornea and epidermis, as well as the outer root sheath of hair follicles. In corneal epithelium, the transgene expression causes decreased expression of adhesion molecule BP180 and defective hemidesmosomes, leading to detachment of corneal epithelium from the underlying stroma, which in turn causes blisters, wounds and an inflammatory response. After a period of epithelial thinning, the corneal epithelium undergoes differentiation to an epidermis-like structure. The K14-DN-Clim mice also develop progressive hair loss due to dysfunctional hair follicles that fail to generate hair shafts. The number of hair follicle stem cells is decreased by at least 50% in K14-DN-Clim mice, indicating that Clims are required for hair follicle stem cell maintenance. We hypothesize that Clim2 is an essential co-factor for the LIM homeodomain factor Lhx2, which was previously shown to play a role in hair follicle stem cell maintenance. Together, these data indicate that Clim proteins play important roles in the homeostasis of corneal epithelium and hair follicles. Keywords: Comparison of wild-type and transgenic skin tissue
2007-06-23 | GSE8227 | GEO
Project description:Gene expression of the combined effect of PDX1 and dominant-negative REST (DN-REST) on primary pancreatic exocrine cells
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Project description:The iPSC reprogramming is very inefficient and has an early stochastic stage. The cause of the low efficiency and stochastic nature are poorly understood. The bromo- and extra-terminal domain (BET) proteins have impacts on cellular reprogramming, but the molecular mechanisms are elusive. Here we show that the reprogramming factors cause dramatic reprogramming stresses including massive transcriptional turbulence, massive and random dysregulation of stress response genes, cell cycle impairment, and cytotoxicity. BET dominant negative (DN) mutants lacking the characteristic ET and bromo- domain enhanced iPSC reprogramming and downregulated a large set of stress response genes over-activated by the reprogramming factors. These DN BET mutants also restored the cell cycle profile and mitotic genes impaired by the reprogramming factors, and mitigate the reprogramming-associated cytotoxicity. The DN BET fragments additionally reduced illegitimate transcriptional reprogramming imposed by the reprogramming factors. Both the DN BET mutants and the BET chemical inhibitors target a similar set of the stress response genes in the reprogramming cells although their targeting mechanism are different. In human naive fibroblasts, these DN BET fragments also commonly target a large set of stress response genes including inflammatory genes, implying general roles of BET proteins in stress responses. These DN BET peptides constitute a novel approach to targeting BET proteins for disease managements.
2023-01-08 | GSE203207 | GEO
Project description:Transcriptome analysis was performed from human U87 glioblastoma cell clones: U87 IRE1.NCK DN (U87dn, IRE1 dominant negative) and U87 control (U87ctrl, empty plasmid). Cells were grown in DMEM supplemented with 10% FBS and glutamine for 16 hours in culture prior mRNA isolation and analyses U87dn cells expressing a dominant negative transgene of IRE1alpha were compared to U87ctrl cells transfected with the corresponding empty plamid to identify genes associated to tumor invasion and angiogenesis.
2010-08-08 | E-GEOD-22385 | biostudies-arrayexpress
Project description:To identify the potential regulators in the progression of diabetic nephropathy (DN), we performed RNA sequencing of blood samples from healthy volunteers, patients with T2D, and patients with DN. Further analyses revealed that FTO was significantly downregulated in blood samples of T2D and DN patients, while the expression of other erasers, writers or readers remained unchanged between disease and healthy groups . Our study thus provides potential molecular mechanisms for DN progression and association of differential gene expression with the functional and structural changes observed in patients with DN.
2024-01-13 | GSE154881 | GEO
Project description:Transcriptome analysis was performed from human U87 glioblastoma cell clones: U87 IRE1.NCK DN (U87dn, IRE1 dominant negative) and U87 control (U87ctrl, empty plasmid). Cells were grown in DMEM supplemented with 10% FBS and glutamine for 16 hours in culture prior mRNA isolation and analyses
2010-08-08 | GSE22385 | GEO