Glucocorticoids Unmask Silent Non-Coding Genetic Risk Variants for Common Diseases [ChIP-seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE185928 | GEO | 2022/11/16
REPOSITORIES: GEO
Similar Datasets
Project description:30 B-lymphoblastoid cell lines (LCLs) with genome-wide genotype data were treated with hydrocortisone (GR agonist) and CORT108297 (GR modulator), followed by RNA-seq to identify PGx-eQTLs. We then integrated GR chromatin immunoprecipitation-sequencing (ChIP-seq) to characterize the epigenetic function of PGx-eQTLs that interfere with GR response elements. We also applied a high-throughput enhancer assay (STARR-seq) using PGx-eQTL loci DNA sequences to “scan” for drug-dependent SNPs.
2022-11-16 | GSE189453 | GEO
Project description:30 B-lymphoblastoid cell lines (LCLs) with genome-wide genotype data were treated with hydrocortisone (GR agonist) and CORT108297 (GR modulator), followed by RNA-seq to identify PGx-eQTLs. We then integrated GR chromatin immunoprecipitation-sequencing (ChIP-seq) to characterize the epigenetic function of PGx-eQTLs that interfere with GR response elements. We also applied a high-throughput enhancer assay (STARR-seq) using PGx-eQTL loci DNA sequences to “scan” for drug-dependent SNPs.
2022-11-16 | GSE185908 | GEO
Project description:30 B-lymphoblastoid cell lines (LCLs) with genome-wide genotype data were treated with hydrocortisone (GR agonist) and CORT108297 (GR modulator), followed by RNA-seq to identify PGx-eQTLs. We then integrated GR chromatin immunoprecipitation-sequencing (ChIP-seq) to characterize the epigenetic function of PGx-eQTLs that interfere with GR response elements. We also applied a high-throughput enhancer assay (STARR-seq) using PGx-eQTL loci DNA sequences to “scan” for drug-dependent SNPs.
2022-11-16 | GSE185939 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-11-16 | GSE185941 | GEO
Project description:Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches. GR and NFkB ChIP-seq in lymphoblastoid cell lines treated with either dexamethasone or EtOH (vehicle for dexamethasone) for 1 hour.
2013-04-01 | E-GEOD-45638 | biostudies-arrayexpress
Project description:Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches. Total RNA obtained from lymphoblastoid cell lines treated with either dexamethasone or EtOH (vehicle for dexamethasone) for 2, 4, 8, 12, 16, or 24 hours.
2013-04-01 | E-GEOD-44248 | biostudies-arrayexpress
Project description:Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches.
2013-04-01 | GSE44248 | GEO
Project description:Glucocorticoids (GCs) are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR), which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI) and 4 Tuscans (TSI) lymphoblastoid cell lines (LCLs), we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative) depending on the presence of specific interacting TFs. Accordingly, when we performed ChIP-seq for GR and NF-kB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches.
2013-04-01 | GSE45638 | GEO
Project description:HGU133+2.0 Microarray on TNBC cells (MDA-MB-231) treated for 4, 8, or 12h with vehicle, 100nM dexamethasone, 100nM Dex/100nM Mifepristone, or 100nM Dex/100nM CORT108297 Purpose: Although high glucocorticoid receptor (GR) expression in early-stage estrogen receptor (ER)-negative breast cancer (BC) is associated with shortened relapse-free survival (RFS), how associated GR transcriptional activity contributes to aggressive BC behavior is not well understood. Using potent GR antagonists and primary tumor gene expression data, we sought to identify a tumor-relevant gene signature based on GR activity that would be more predictive than GR expression alone. Design: Global gene expression and GR ChIP-sequencing were performed to identify GR-regulated genes inhibited by two chemically distinct GR antagonists, mifepristone and CORT108297. Differentially expressed genes from MDA-MB-231 cells were cross-evaluated with significantly expressed genes in GR-high versus GR-low ER-negative primary BCs. The resulting subset of GR targeted genes was analyzed in two independent ER-negative BC cohorts to derive and then validate the GR activity signature (GRsig). Results: Gene expression pathway analysis of glucocorticoid-regulated genes (inhibited by GR antagonism) revealed cell survival and invasion functions. GR ChIP-seq analysis demonstrated that GR antagonists decreased GR chromatin association for a subset of genes. A GRsig comprised of n=74 GR activation-associated genes (also reversed by GR antagonists) was derived from an adjuvant chemotherapy-treated Discovery cohort and found to predicted probability of relapse in a separate Validation cohort (HR=1.9; p= 0.012). Conclusions: The GRsig discovered herein identifies high-risk ER-negative/GR-positive BCs most likely to relapse despite administration of adjuvant chemotherapy. Because GR antagonism can reverse expression of these genes, we propose that addition of a GR antagonist to chemotherapy may improve outcome of these high-risk patients.
2018-04-25 | GSE113571 | GEO
Project description:Appropriate gene expression patterns form the basis for bone microcirculatory endothelial cellsM-bM-^@M-^Y function and bone morphology. Although previous studies have elucidated the impact of hydrocortisone on bone microcirculatory endothelial cellsM-bM-^@M-^Y specific gene expression, the exact differential transcriptomes and comprehensive gene expression profiles remain unknown. We have investigated the mRNA and lncRNA expression patterns before and after hydrocortisone administration of bone microcirculatory endothelial cells. At mRNAs level totally 518 differentially expressed genes were identified. Furthermore, we identified 73 upregulated and 166 downregulated long non-coding RNAs after administration of hydrocortisone. These RNAs appeared to be highly important to gene co-expression network. Transcriptomic analysis of bone microcirculatory endothelial cells from human samples is highly informative due to their relevance to the large number of expressed genes. Our study provides a very valuable basis for investigation of genes, regulation and their co-expression network contributing to hydrocortisone induced disorders. Two-condition experiment, hydrocortisone treated vs. untreated bone microcirculatory endothelial cells. Biological replicates: 8 control replicates, 8 treated replicates.
2015-01-01 | E-GEOD-60332 | biostudies-arrayexpress