Effect of FOXO3 on GR Signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE190235 | GEO | 2022/11/18
REPOSITORIES: GEO
Similar Datasets
Project description:To identify cross-talk between the cytoplasmic kinase AMPK and the nuclear receptor, glucocorticoid receptor, during inflammatory responses, bone-marrow-derived macrophages lacking the catalytic domain of AMPK, AMPKa1, were exposed to vehicle, dexamethasone, a synthetic glucocorticoid, lipopolysaccharide, crushed muscle extract (damage-associated molecular patterns) or a combination of the inflammatory stimulus and dexamethasone.
2022-01-12 | GSE167382 | GEO
Project description:Glucocorticoids are primary stress hormones and their synthetic derivatives are widely used clinically. The therapeutic efficacy of these steroids is limited by severe side effects and glucocorticoid resistance. Multiple glucocorticoid receptor (GR) isoforms are produced by alternative translation initiation; however, the role individual isoforms play in controlling tissue-specific responses to glucocorticoids in vivo is unknown. We have generated knockin mice that exclusively express the most active receptor isoform, GR-C3. The GR-C3 knockin mice die at birth due to respiratory distress but can be completely rescued by antenatal glucocorticoid administration. To evaluate the GR-C3 transcriptome, we prepared mouse embryonic fibroblasts (MEFs) from E12.5 wild-type (WT) and GR-C3 knockin embryos and treated the cells with vehicle or the synthetic glucocorticoid Dexamethasone (Dex) for 6 hours. The GR-C3 isoform was found to have a markedly different gene-regulatory profile than GR in WT MEFs.
2018-04-23 | GSE103675 | GEO
Project description:Glucocorticoids are primary stress hormones that regulate many physiological processes, and synthetic derivatives of these molecules and are widely used in the clinic. The cellular response to glucocorticoids is remarkably diverse; however, the molecular factors that govern tissue specificity are poorly understood. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR). To discover new proteins that interact with GR and modulate its function, we performed a yeast 2 hybrid assay using as bait the hinge region of GR. The MyoD family inhibitor domain-containing (MDFIC) protein was identified as a binding partner for GR. Knockdown of MDFIC in A549 cells alters the GR transcriptome. To further investigate the functional effect of MDFIC on the GR transcriptome, we performed a genome-wide microarray in COS-1 cells that were transfected with GR alone or GR and MDFIC. The transfected cells were treated with vehicle or the synthetic glucocorticoid Dexamethasone (Dex) for 6 hours. Overexpression of MDFIC was found to expand the GR transcriptome.
2017-04-07 | GSE93899 | GEO
Project description:Glucocorticoids are primary stress hormones that regulate many physiological processes, and synthetic derivatives of these molecules and are widely used in the clinic. The cellular response to glucocorticoids is remarkably diverse; however, the molecular factors that govern tissue specificity are poorly understood. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR). To discover new proteins that interact with GR and modulate its function, we performed a yeast 2 hybrid assay using as bait the hinge region of GR. The MyoD family inhibitor domain-containing (MDFIC) protein was identified as a binding partner for GR. Knockdown of MDFIC in A549 cells alters the GR transcriptome. Overexpression of MDFIC with GR in COS-1 cells also modulates the GR transcriptome by expanding the number of genes regulated in response to glucocorticoid treatment. Our findings in A549 cells suggest that MDFIC alters the gene regulatory profile of GR by modulating receptor phosphorylation at several residues, including S211. To further investigate the molecular link between MDFIC-mediated effects on GR phosphorylation at S211 and alterations in the GR transcriptome, we performed a genome-wide microarray in COS-1 cells that were transfected with the GR phosphorylation mutant S211A or S211A and MDFIC. The transfected cells were treated with vehicle or the synthetic glucocorticoid Dexamethasone (Dex) for 6 hours. The ability of MDFIC to expand the GR transcriptome was attenuated in cells expressing S211A mutant.
2017-04-07 | GSE93900 | GEO
Project description:We performed STARR-seq with synthetic libraries (synSTARR-seq) in GR18 cell line (derived from U2OS ATTC:HTB-96, stably transfected with an expression construct for GR), upon glucocorticoid (dexamethasone) or vehicle (ethanol) treatment. The synthetic libraries are variants of the glucocorticoid receptor binding sites (GBS). The "GBS half site" library contains 8 consecutive randomized nucleotides within the core binding sites, while the "Cgt/Sgk library" contains 5 consecutive randomized nucleotides on the flank of the GBS.
2018-10-29 | E-MTAB-6737 | biostudies-arrayexpress
Project description:Glucocorticoids are critical components of combination chemotherapy regimens in pediatric acute lymphoblastic leukemia (ALL). However, the signaling pathways regulating apoptosis in glucocorticoid-treated lymphoid cells remain unclear. In this study, pediatric ALL patient-derived xenograft inherently sensitive to glucocorticoids were exposed to dexamethasone in vivo. Whole-genome GR binding sites and histone acetylation status were detected using chromatin immunoprecipitation sequencing analyses. This provided a global understanding of dexamethasone-induced DNA modulations in ALL cells in vivo, which is likely to be important in the understanding of mechanisms of glucocorticoid response in lymphoid malignancies. One xenograft (ALL-54) was derived from a patient of dexamethasone-good responder. The xenograft was innoculated into 2 NOD/SCID mice, and treated with dexamethasone (15 mg/kg) or vehicle control. Binding of glucocorticoid receptor (GR), histone acetylation and IgG control in spleen-harvest xenograft samples were detected using ChIP-seq.
2014-12-18 | E-GEOD-58266 | biostudies-arrayexpress
Project description:Glucocorticoids are primary stress hormones that regulate many physiological processes, and synthetic derivatives of these molecules and are widely used in the clinic. The cellular response to glucocorticoids is remarkably diverse; however, the molecular factors that govern tissue specificity are poorly understood. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR). To discover new proteins that interact with GR and modulate its function, we performed a yeast 2 hybrid assay using as bait the hinge region of GR. The MyoD family inhibitor domain-containing (MDFIC) protein was identified as a binding partner for GR. To investigate the function of the GR-MDFIC interaction, we performed a genome-wide microarray in intact and MDFIC deficient A549 cells that were treated with the synthetic glucocorticoid Dexamethasone (Dex). A large cohort of genes was differentially regulated by GR depending on the presence or absence of MDFIC. These findings identify a new binding partner for cytoplasmic GR that modulates the receptor transcriptome and contributes to the tissue specific actions of glucocorticoids.
2017-04-07 | GSE86115 | GEO
Project description:Effect of FOXO3 on GR Signaling
| PRJNA786489 | ENA
Project description:The aim of the experiment was to gain insight into the selective anti-inflammatory action of the glucocorticoid receptor modulator AZD9567 in comparison with the classical synthetic glucocorticoid dexamethasone. To this end, the transcriptional profile of macrophage RAW 264.7 cells treated with dexamethasone or AZD9567 in the presence or absence of inflammatory response (elicited by lipopolysaccharide treatment) was identified.
2023-06-30 | E-MTAB-12816 | biostudies-arrayexpress
Project description:FOXO transcription factors are key players in diverse cellular responses affecting tumorigenesis, stem cell maintenance and lifespan. To gain insight into mechanisms of FOXO regulated gene expression, we studied genome-wide effects of FOXO3 activation. Profiling RNA polymerase II (RNAPII) changes shows FOXO3 regulates gene expression through transcription initiation. Correlative analysis of FOXO3 and RNAPII ChIP-seq profiles demonstrates FOXO3 to act as a transcriptional activator. Furthermore, this analysis reveals a significant part of FOXO3 gene regulation proceeds through enhancer regions. FOXO3 binds to and activates enhancers as shown by the presence of and changes in enhancer-specific histone modifications and RNAPII occupancy. In addition, FOXO3-mediated enhancer regulation correlates with regulation of adjacent genes and existence of chromatin loops between FOXO3 bound enhancers and regulated genes. Combined, our data elucidate how FOXOs regulate gene transcription and provide insight into mechanisms by which FOXOs can induce different gene expression programs depending on chromatin architecture. seven 4C view point were analyzed on DLD1 colon carcinoma cells containing 4OH-Tamoxifen inducible FOXO3A3-ER (DL23 cells, Kops et al., 2002, Mol Cell Biol), to investigate 3D topology around FOXO3 bound regions and FOXO3 regulated genes before and 4 hours after addition of tamoxifen. 4C procedure, as published before (Splinter et al., 2001, Genes Dev). Cells are cross linked using 1% formaldehyde for 10min at room temperature, nuclei are isolated, after which chromatin is digested with DpnII and subsequently ligated under diluted conditions. After reversal of the cross links the DNA is purified and treated with the second restriction enzyme treatment (Csp). After a second re-ligation step the sample is purified and ligated fragments are analyzed by inverse PCR.
2012-12-30 | E-GEOD-36835 | biostudies-arrayexpress