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ABSTRACT:
PROVIDER: PRJNA195456 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genetic, functional and molecular features of glucocorticoid receptor binding (sequencing)
| PRJNA195462 | ENA
Project description:Genetic, functional and molecular features of glucocorticoid receptor binding (expression)
| PRJNA189242 | ENA
Project description:The glucocorticoid receptor (GR) binds the human genome at >10,000 sites, but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation (ChIP) in A549 cells. 13% of GBSs assayed had GC-induced activity. The responsive sites were defined by direct GR binding via a GC response element (GRE) and exclusively increased reporter- gene expression. Meanwhile, most GBSs lacked GC-induced reporter activity. The non-responsive sites had epigenetic features of steady state enhancers and clustered around direct GBSs. Together, our data support a model in which clusters of GBSs observed with ChIP-seq reflect interactions between direct and tethered GBSs over tens of kilobases. We further show that those interactions can synergistically modulate the activity of direct GBSs, and may therefore play a major role in driving gene activation in response to GCs. Glucoroticoid receptor binding site chip-seq libraries were cloned into STARR-seq for massively parallel functional analysis. The results were confirmed by ChIP-Exo performed on the GR in A549 cells treated with 100 nM dexamethasone for one hour. Dnase-seq was performed on A549 cells treated for 1 h with dexamethasone or ethanol.
2016-08-25 | E-GEOD-77869 | biostudies-arrayexpress
Project description:The glucocorticoid receptor (GR) binds the human genome at >10,000 sites, but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation (ChIP) in A549 cells. 13% of GBSs assayed had GC-induced activity. The responsive sites were defined by direct GR binding via a GC response element (GRE) and exclusively increased reporter- gene expression. Meanwhile, most GBSs lacked GC-induced reporter activity. The non-responsive sites had epigenetic features of steady state enhancers and clustered around direct GBSs. Together, our data support a model in which clusters of GBSs observed with ChIP-seq reflect interactions between direct and tethered GBSs over tens of kilobases. We further show that those interactions can synergistically modulate the activity of direct GBSs, and may therefore play a major role in driving gene activation in response to GCs. Glucoroticoid receptor binding site chip-seq libraries were cloned into STARR-seq for massively parallel functional analysis. The results were confirmed by ChIP-Exo performed on the GR in A549 cells treated with 100 nM dexamethasone for one hour. This dataset [8] contains ChIP-seq data for A549 cells treated with DEX or EtOH for 3 hours.
2016-08-25 | E-GEOD-79431 | biostudies-arrayexpress
Project description:The glucocorticoid receptor (GR) binds the human genome at >10,000 sites, but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation (ChIP) in A549 cells. 13% of GBSs assayed had GC-induced activity. The responsive sites were defined by direct GR binding via a GC response element (GRE) and exclusively increased reporter- gene expression. Meanwhile, most GBSs lacked GC-induced reporter activity. The non-responsive sites had epigenetic features of steady state enhancers and clustered around direct GBSs. Together, our data support a model in which clusters of GBSs observed with ChIP-seq reflect interactions between direct and tethered GBSs over tens of kilobases. We further show that those interactions can synergistically modulate the activity of direct GBSs, and may therefore play a major role in driving gene activation in response to GCs. Glucoroticoid receptor binding site chip-seq libraries were cloned into STARR-seq for massively parallel functioal analysis. The results were confirmed by ChIP-Exo performed on the GR in A549 cells treated with 100 nM dexamethasone for one hour. This dataset [6] contains the ChIP exo data from cells treated with 100 nM DEX.
2016-08-25 | E-GEOD-79429 | biostudies-arrayexpress
Project description:The glucocorticoid receptor (GR) binds the human genome at >10,000 sites, but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation (ChIP) in A549 cells. 13% of GBSs assayed had GC-induced activity. The responsive sites were defined by direct GR binding via a GC response element (GRE) and exclusively increased reporter- gene expression. Meanwhile, most GBSs lacked GC-induced reporter activity. The non-responsive sites had epigenetic features of steady state enhancers and clustered around direct GBSs. Together, our data support a model in which clusters of GBSs observed with ChIP-seq reflect interactions between direct and tethered GBSs over tens of kilobases. We further show that those interactions can synergistically modulate the activity of direct GBSs, and may therefore play a major role in driving gene activation in response to GCs. Glucoroticoid receptor binding site chip-seq libraries were cloned into STARR-seq for massively parallel functional analysis. The results were confirmed by ChIP-Exo performed on the GR in A549 cells treated with 100 nM dexamethasone for one hour. This dataset [3] contains the results of RNA-seq performed on A549 cells treated with DEX or EtOH for 3 hours.
2016-08-25 | E-GEOD-79426 | biostudies-arrayexpress
Project description:The glucocorticoid receptor (GR) is a nuclear hormone receptor critical to the regulation of energy metabolism and the inflammatory response. The actions of GR have been shown to be highly dependent on context. Here, we performed GR ChIP-seq in mouse liver to demonstrate the necessity for liver lineage-determining factor hepatocyte nuclear factor 4A (HNF4A) in defining tissue-specificity of GR action. In normal liver, the HNF4 motif lies adjacent to the glucocorticoid response element (GRE) at GR binding sites found within regions of open chromatin. In the absence of HNF4A, the liver GR cistrome is remodelled, with both loss and gain of GR recruitment evident. Lost sites are characterised by HNF4 motifs and weak GRE motifs. Gained sites are characterised by strong GRE motifs, and typically show GR recruitment in non-liver tissues. The functional importance of these HNF4A-regulated GR sites is further demonstrated by evidence of an altered transcriptional response to glucocorticoid treatment in the Hnf4a-null liver.
2021-04-09 | E-MTAB-10224 | biostudies-arrayexpress
Project description:Glucocorticoid (GC) response elements (GREs) are genomic segments that confer GC-regulated transcription by recruiting hormone-bound glucocorticoid receptor (GR) and nucleating assembly of transcriptional regulatory complexes (TRCs). The locations of GR binding, the functionality of those GR occupied regions (GORs) as GREs, and the molecular features and spatial organization that characterize active GREs are gene-, cell- and physiological-context specific, and poorly understood. Moreover, identification of the gene(s) targeted for regulation by a given GRE has been inferred by proximity, or examined outside the normal chromosomal context, rather than rigorously validated. We approached these issues in two human cell lines with distinct tissue origins, treated or not with a hormonal ligand that activates GR.
2020-12-18 | GSE163398 | GEO
Project description:Glucocorticoid Receptor and Androgen Receptor DNA binding in LREX'
| PRJNA223314 | ENA
Project description:SNPs affecting disease risk often reside in non-coding genomic regions. Here we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPARγ, a nuclear receptor for antidiabetic drugs. Many such SNPs alter binding motifs for PPARγ or cooperating factors, and functionally regulate nearby genes whose expression is strain-selective and imbalanced in heterozygous F1 mice. Moreover, genetically-determined binding of PPARγ accounts for mouse strain-specific transcriptional effects of TZD drugs, providing proof-of- concept for personalized medicine related to nuclear receptor genomic occupancy. In human fat, motif-altering SNPs cause differential PPARγ binding, provide a molecular mechanism for some expression quantitative trait loci, and are risk factors for dysmetabolic traits in genome- wide association studies. One PPARγ motif-altering SNP is associated with HDL levels and other metabolic syndrome parameters. Thus, natural genetic variation in PPARγ genomic occupancy determines individual disease risk and drug response. 6 ChIP-seq experiments conducted in mice and 5 in human subjects. Deep sequencing carried out using Illumina HiSeq2000 and the Solexa Analysis Pipeline eWAT; epididymal White Adipose Tissue iWAT; inguinal White Adipose Tissue 12wLFD; mice were fed a control low fat diet (Research Diet D12450B) chow; mice were fed standard rodent chow Diet GR; Glucocorticoid receptor
2015-07-02 | E-GEOD-64458 | biostudies-arrayexpress