Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-21048
PROVIDER: PRJNA126431 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Glucocorticoids control expression of a large number of genes after binding to the glucocorticoid receptor (GR). Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in regulation of gene expression, we performed gene expression profiling in liver of prednisolone-treated wild type (WT) and genetically engineered mice that have lost the ability to form GR-dimers (GRdim). Mice carrying a wild type (WT) glucocorticoid receptor or a dimerization-defective glucocorticoid receptor (GRdim) were treated subcutaneous with vehicle or prednisolone (1mg/kg) and sacrificed 150 minutes later. From the livers of these mice total RNA was extracted, processed and hybridized on Affymetrix microarrays. In total 24 mice (6 vehicle-treated WT mice, 6 prednisolone-treated WT mice, 6 vehicle-treated GRdim mice and 6 prednisolone-treated GRdim mice) were included in the study.
2010-06-08 | E-GEOD-21048 | biostudies-arrayexpress
Project description:Prednisolone-induced differential gene expression in liver of mice carrying the wild type or a dimerization-defective glucocorticoid receptor
2015-09-15 | E-GEOD-21048 | ExpressionAtlas
Project description:Glucocorticoids control expression of a large number of genes after binding to the glucocorticoid receptor (GR). Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in regulation of gene expression, we performed gene expression profiling in liver of prednisolone-treated wild type (WT) and genetically engineered mice that have lost the ability to form GR-dimers (GRdim).
2010-05-20 | GSE21048 | GEO
Project description:Analysis of the effect of Prednisolone in mouse splenocytes with and without Ikzf1 at gene expression level. The hypothesis tested in the present study was that loss of Ikzf1 affects the induction and repression of the Glucocorticoid receptor target genes. Results provide important information of the differentially expressed genes regulated by Ikzf1 upon Prednisolone treatment, explaining the resistance towards Glucocorticoid-induced apoptosis in splenocytes harboring Ikzf1 loss.
2015-02-04 | GSE65554 | GEO
Project description:Analysis of the effect of Prednisolone in mouse splenocytes with and without Ikzf1 at gene expression level. The hypothesis tested in the present study was that loss of Ikzf1 affects the induction and repression of the Glucocorticoid receptor target genes. Results provide important information of the differentially expressed genes regulated by Ikzf1 upon Prednisolone treatment, explaining the resistance towards Glucocorticoid-induced apoptosis in splenocytes harboring Ikzf1 loss. Total RNA was obtained from WT and Ikzf1+/- splenocytes subjected to 16 hours Prednsiolone treatment compared to untreated cells.
2015-02-04 | E-GEOD-65554 | biostudies-arrayexpress
Project description:Prednisolone is a potent anti-inflammatory glucocorticoid (GC) but chronic use is hampered by metabolic side effects. Although GCs are predominantly prescribed for treatment of inflammatory conditions, little is known about their long-term effects on gene-expression in-vivo during inflammation. Here, we aimed to identify genes underlying prednisolone-induced metabolic side effects in a complex in-vivo inflammatory setting after long-term treatment. We performed whole-genome expression profiling in liver and muscle from arthritic and non-arthritic mice treated with several doses of prednisolone for three weeks.
2013-11-10 | E-MTAB-1765 | biostudies-arrayexpress
Project description:A mutation in the dimerization domain of the mouse glucocorticoid receptor (GR), dim1, has recently been shown to bind DNA and regulate gene expression. To expand these studies we created a stable osteosarcoma (U-2 OS) cell line expressing four mutations in the dimerization domain of the human GR, dim4 (N454D, A458T, R460D, D462C), and used whole human genome microarray analysis to compare differences in gene regulation between vehicle treated (CON) and those treated with the glucocorticoid receptor agonist dexamethasone (DEX) at 100nM concentration for 6 hours. Gene expression in U-2 OS hGRdim4 cells was measured after a 6 hour treatment with 100nM dexamethasone or vehicle (control) and the dexamethsone (dex) treated cells were compared to vehicle treated cells. The experiment was performed in triplicate.
2011-12-22 | E-GEOD-26857 | biostudies-arrayexpress
Project description:A mutation in the dimerization domain of the mouse glucocorticoid receptor (GR), dim1, has recently been shown to bind DNA and regulate gene expression. To expand these studies we created a stable osteosarcoma (U-2 OS) cell line expressing four mutations in the dimerization domain of the human GR, dim4 (N454D, A458T, R460D, D462C), and used whole human genome microarray analysis to compare differences in gene regulation between vehicle treated (CON) and those treated with the glucocorticoid receptor agonist dexamethasone (DEX) at 100nM concentration for 6 hours.
2011-12-22 | GSE26857 | GEO
Project description:Cortisol, the central stress hormone in humans, activates the glucocorticoid receptor (GR). Anti-inflammatory effects are the most important pharmaceutical effects mediated by the GR. Inasmuch as electrophilic cyclopentenone prostaglandin 15-deoxy-M-NM-^T12,14-prostaglandin J2 (15d-PGJ2) has potent anti-inflammatory properties and activates the SUMOylation pathway, we have investigated the effect of 15d-PGJ2 on glucocorticoid signaling and receptor SUMOylation. To this end, we studied isogenic HEK293 cells expressing either wild-type GR or SUMOylation-defective GR. Interestingly, 15d-PGJ2 triggered SUMO-2/3 modification in the primary SUMOylation sites of the GR. Gene expression profiling and pathway analyses indicate that 15d-PGJ2 inhibits GR signaling in a genome-wide fashion that is significantly dependent on the GR SUMOylation sites. Chromatin immunoprecipitation assays showed that the repressive effect of 15d-PGJ2 on GR target gene expression occurs in parallel with the inhibition of receptor binding to the target gene chromatin. Furthermore, depletion of the sole SUMO E2 conjugase UBC9 from HEK293 cells confirmed the involvement of active SUMOylation in the regulatory process. Taken together, our data indicate that GR SUMOylation modulates the glucocorticoid signaling during acute cell stress. Our data also suggest that GR SUMOylation modulates crosstalk of the glucocorticoid signaling with other transcription factors that are responsive to cell stress. Total RNA isolated from isogenic HEK293 cell lines stably expressing either wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR) treated with 100 nM of dexamethasone (dex) in the presence or absence of 5 M-BM-5M 15d-PGJ2 for 6h. All conditions are performed in triplicate
2014-06-30 | E-GEOD-54087 | biostudies-arrayexpress
Project description:Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and glucocorticoid resistance in leukemia cells confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 newly diagnosed ALL patients and found significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases.
2015-03-24 | GSE67043 | GEO