E-GEOD-6197
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA100683
PROVIDER: E-GEOD-6197 | ExpressionAtlas | 2015-10-13
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:The glucocorticoid receptor (GR) is a transcription factor that localizes to the nucleus and reuglates gene expression upon binding of a glucocorticoid ligand such as dexamethasone. We perform nascent transcriptional profiling of C7 ALL cells following treatment with dexamethasone to evaluate the immediate transcriptional effects of GR. We find 51 dynamic genes (46 activated, 5 repressed) after 1 hour treatment and 141 dynamic genes (70 activated and 71 repressed) after 4 hour treatment. We input RNA polymerase density in pause and gene body regions into a mathematical model designed to quantify rate changes of individual transcriptional steps. We find that dexamethasone treatment primarily activates genes by inducing pause release rate.
2022-12-04 | GSE219041 | GEO
Project description:Glucocorticoids induce rapid apoptosis of rat primary thymocytes through mechanisms requiring altered gene expression. The determination of genes regulating glucocorticoid-induced apoptosis of lymphocytes has received considerable attention. However, the role of specific non-coding microRNAs in the regulation of glucocorticoid-induced apoptosis of lymphocytes is poorly defined. Using deep sequencing analysis, we have identified microRNAs differentially expressed during glucocorticoid-induced apoptosis of rat primary thymocytes. We have also identified numerous loci that harbor probable novel microRNAs. Furthermore, we have validated the glucocorticoid-responsive expression of 2 novel microRNAs in the apoptotic rat primary thymocyte. These 2 novel microRNAs are predicted to target numerous messenger RNAs throughout the genome. Using whole genome expression analysis, we now seek to correlate the altered expression of these novel microRNAs with the expression of their predicted target mRNAs during glucocorticoid-induced apoptosis. Changes in gene expression during glucocorticoid-induced apoptosis of rat primary thymocyes (3 biological replicates) were measured after 6 hours of 100nM dexamethasone treatment in-vitro.
2014-03-26 | E-GEOD-45560 | biostudies-arrayexpress
Project description:ARGLU1 is a Transcriptional Coactivator and Splicing Regulator Important for Stress Hormone Signaling and Development Stress hormones bind and activate the glucocorticoid receptor (GR) in many tissues including the brain. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies show that the glutamate rich C-terminus of ARGLU1 coactivates multiple nuclear receptors including the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing factors and binds to RNA. RNA-seq of neuronal cells depleted of ARGLU1 revealed significant changes in the expression and alternative splicing of distinct genes involved in neurogenesis. Loss of ARGLU1 is embryonic lethal in mice, and knockdown in zebrafish causes neurodevelopmental and heart defects. Treatment with dexamethasone, a GR activator, also induces changes in the pattern of alternatively spliced genes, many of which were lost when ARGLU1 was absent. Importantly, the genes found to be alternatively spliced in response to glucocorticoid treatment were distinct from those under transcriptional control by GR, suggesting an additional mechanism of glucocorticoid action is present in neuronal cells. Our results thus show that ARGLU1 is a novel factor for embryonic development that modulates basal transcription and alternative splicing in neuronal cells with consequences for glucocorticoid signaling.
2019-02-15 | PXD012406 | Pride
Project description:ARGLU1 is a Transcriptional Coactivator and Splicing Regulator Important for Stress Hormone Signaling and Development Stress hormones bind and activate the glucocorticoid receptor (GR) in many tissues including the brain. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies show that the glutamate rich C-terminus of ARGLU1 coactivates multiple nuclear receptors including the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing factors and binds to RNA. RNA-seq of neuronal cells depleted of ARGLU1 revealed significant changes in the expression and alternative splicing of distinct genes involved in neurogenesis. Loss of ARGLU1 is embryonic lethal in mice, and knockdown in zebrafish causes neurodevelopmental and heart defects. Treatment with dexamethasone, a GR activator, also induces changes in the pattern of alternatively spliced genes, many of which were lost when ARGLU1 was absent. Importantly, the genes found to be alternatively spliced in response to glucocorticoid treatment were distinct from those under transcriptional control by GR, suggesting an additional mechanism of glucocorticoid action is present in neuronal cells. Our results thus show that ARGLU1 is a novel factor for embryonic development that modulates basal transcription and alternative splicing in neuronal cells with consequences for glucocorticoid signaling.
2019-02-15 | PXD012555 | Pride
Project description:Glucocorticoids, which activate glucocorticoid receptor signaling and thus modulate gene expression, are widely used to treat asthma. Glucocorticoids exert their therapeutic effects in part through modulating airway smooth muscle structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. Here, we used transcription profiling to characterize the effects of a potent glucocorticoid, dexamethasone, on cultured human airway smooth muscle gene expression at 4 and 24 hours. This study examined differential gene expression induced by treatment of cultured human airway smooth muscle cells with dexamethasone. There were 3 groups of samples and each group had 4 biological replicates. Group 1 was no treatment, Group 2 was dexamethasone (dex) treatment for 4 hours, Group 3 was dex treatment for 24 hours. Cultures were synchronized so harvest occurred at the same time for all three groups. 2 samples are not included in this analysis (based on unsupervised clustering of samples and diagnostic plots).
2011-12-10 | E-GEOD-34313 | biostudies-arrayexpress
Project description:Glucocorticoids are an essential component of the treatment of lymphoid malignancies and resistance to glucocorticoid therapy constitutes a prominent clinical problem in relapsed and refractory lymphoblastic leukemias. Constitutively active NOTCH signaling is involved in the pathogenesis of over 50% of T-cell lymphoblastic leukemia (T-ALL) which harbor activating mutations in the NOTCH1 gene. Aberrant NOTCH1 signaling has been shown to protect normal thymocytes from glucocorticoid induced cell death. Here we analyzed the interaction of glucocorticoid therapy with inhibition of NOTCH signaling in the treatment of T-ALL. Gamma-secretase inhibitors (GSI), which block the activation of NOTCH receptors, amplified the transcriptional changes induced by glucocorticoid treatment, including glucocorticoid receptor autoinduction and restored sensitivity to dexamethasone in glucocorticoid-resistant T-ALL cells. Apoptosis induction upon inhibition of NOTCH signaling and activation of the glucocorticoid receptor was dependent on transcriptional upregulation of BIM and subsequent activation of the mitochondrial/intrinsic cell death pathway. Finally, we used a mouse xenograft model of T-ALL to demonstrate that combined treatment with dexamethasone and a GSI results in improved antileukemic effects in vivo. These studies provide insight in the mechanisms of glucocorticoid resistance and serve as rationale for the use of glucocorticoid and GSIs in combination in the treatment of T-ALL. Experiment Overall Design: Duplicate samples (biologic replicas) from CUTLL1 cells were treated for 24 hours with vehicle only (DMSO), dexamethasone (1microM), a gamma-secretase inhibitor (CompE 100nM) and a combination of dexamethasome plus gamma secretase inhibitor at the same concentrations indicated before. Gene expression profiling was analyzed to identify gene expression signatures assocuated with glucocorticoid treatment (dexamethasone), inhibition of NOTCH1 by gamma secretase inhibitor (CompE) or the combination of both treatments.
2009-01-13 | E-GEOD-7067 | biostudies-arrayexpress
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer frequently associated with activating mutations in NOTCH1. Early studies identified NOTCH1 as an attractive therapeutic target for the treatment of T-ALL through the use of gamma-secretase inhibitors (GSIs). Here, we characterized the interaction between PF-03084014, a clinically-relevant GSI, and dexamethasone in preclinical models of glucocorticoid-resistant T-ALL. Combination treatment of the GSI PF-03084014 with glucocorticoids induced a synergistic antileukemic effect in human T-ALL cell lines and primary human T-ALL patient samples. Molecular characterization of the response to PF-03084014 plus glucocorticoids through gene expression profiling revealed transcriptional upregulation of the glucocorticoid receptor as the mechanism mediating the enhanced glucocorticoid response. Moreover, treatment with PF-03084014 and glucocorticoids in combination was highly efficacious in vivo, with enhanced reduction of tumor burden in a xenograft model of T-ALL. Finally, glucocorticoid treatment was highly effective at reversing PF-03084014-induced gastrointestinal toxicity via inhibition of goblet cell metaplasia. These results suggest that combination of PF-03084014 treatment with glucocorticoids may be well-tolerated and highly active for the treatment of glucorticoid-resistant T-ALL. Duplicate samples of the CUTLL1 T-ALL cell line were treated with vehicle only (DMSO), the gamma-secretase inhibitor PF-03084014 (1 microM), dexamethasone (1 microM), or PF-03084014 (1 microM). plus dexamethasone (1 microM) for 48 hours. Gene expression profiling was analyzed to identify gene expression signatures assocuated with glucocorticoid treatment (dexamethasone), inhibition of NOTCH1 by gamma secretase inhibitor (PF-03084014) or the combination of both treatments.
2011-11-09 | E-GEOD-33562 | biostudies-arrayexpress
Project description:ra15-05_tt1 - tt1-gr - Discover TT1 donwstream targets - An inducible line carrying TT1, an early marker of endothelium development, fused to the rat glucocorticoid receptor (GR), that allows a dexamethasone (DEX)-mediated posttranslational induction of the proteins, has been created. Siliques have been first treated with cycloheximide, an inhibitor of protein synthesis, to prevent indirect transcriptional effects of the inducible TT1 transcription factor. RNA profiling experiments (CATMA microarrays) will be then conducted before and after DEX induction of TT1. These experiments will unveil direct downstream target genes of the TT1 transcription factor.
2019-12-18 | GSE134014 | GEO
Project description:To identify the sequences responsible for recruitment of Glucocorticoid receptor (GR) to individual loci, we performed ChIP-seq in four cell lines : A549 (ATTC:CCL-185), Nalm-6 (ATCC:CRL-1567), immortalized mouse embryonic fibroblasts (MEFs)(PMID 21131905), and immortalized PCAF-/-; GCN5flox/ MEFs (PMID 21131905) upon glucocorticoid treatment (1.5 hrs, 1M dexamethasone).
2016-11-10 | E-MTAB-5113 | biostudies-arrayexpress
Project description:We performed ChIP-seq targeting the glucocorticoid receptor (GR) in the U2OS-GR cell line. The cell line is derived from U2OS ATTC:HTB-96 and stably transfected with an expression construct for rat GR. The cells were treated with 100 nM dexamethasone for 4 hours, washed 2x with PBS and cultured in hormone-free medium for 24 hours before harvest.
2021-05-03 | E-MTAB-9914 | biostudies-arrayexpress