Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA275427 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A1-2 cells treated with 100 nM Dexamethasone or ethanol vehicle for 8h. The ability of steroid hormone receptors to initiate a genetic program is tightly regulated by the chromatin environment of the responsive regions. Using the glucocorticoid receptor (GR) as a model factor for transcriptional initiation, we classified chromatin structure through Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE), a technique designed to identify regulatory regions and open chromatin within the genome. We looked at dynamic changes in FAIRE signals prior to and following activation of GR with its ligand, dexamethesone, specifically at regions of receptor interaction. We have found a distribution of GR responsive regions that respond to activation by varying degrees of chromatin modulation. The majority of regions that demonstrate GR interaction also demonstrate increases in FAIRE signal in response to ligand. Most of these GR responsive regions fell within a narrow window of FAIRE signal in the basal chromatin state, suggesting a preferred chromatin structure for GR recruitment. Supporting this notion, global FAIRE-seq data indicated an enrichment of signal surrounding the GR binding site prior to activation. FAIRE signal induction correlated to an increase in nuclease sensitivity and overall FAIRE signal also represented a general accessibility of the chromatin. Further investigation into the requirement of ATPase-dependent chromatin remodeling showed response element specific effects of Brg-1 knockdown. FAIRE induction was universally decreased by Brg-1 depletion, but to varying degrees in a target specific manner. Taken together, these data suggest classes of nuclear receptor response regions that react to activation through different chromatin regulatory events and identify a novel identifier of chromatin structure that classifies the majority of response elements tested. Experiment performed in triplicate. 3 biological replicates of A1-2 cells treated with dexamethasone and 3 biological replicates of A1-2 cells treated with ethanol
2012-02-28 | E-GEOD-30592 | biostudies-arrayexpress
Project description:Hormone dependent activation of enhancers includes histone hyperacetylation and mediator recruitment. Histone hyperacetylation is often explained by a bimodal switch mod-el, where histone deacetylases (HDACs) disassociates from chromatin and histone acetyl transferases (HATs) are recruited. This model builds on decades of research on steroid re-ceptor regulation of transcription. We have used a genomics approach to study enhancer hyperacetylation by the thyroid hormone receptor (TR) and present a revised model. 1) at poised constitutively TR bound enhancers, HATs occupy chromatin irrespective of thyroid hormone (T3) levels, whereas HDAC occupancy is regulated by T3, suggesting that HDACs functions as a histone acetylation rheostat. 2) at enhancers established in a T3 dependent manner, TR is recruited to chromatin together with HATs. 3) a number of enhancers are hy-peracetylated secondary to TR activation. Collectively, this demonstrates various mechanisms controlling hormone dependent transcription and adds significant details to the otherwise simple bimodal switch model.
2019-07-01 | GSE128535 | GEO
Project description:Transcriptional regulation in response to thyroid hormone (3,5,3´-triiodo-L-thyronine, T3) is a dynamic and cell-type specific process that maintains cellular homeostasis and identity in all tissues. However, our understanding of the mechanisms of thyroid hormone receptor (TR) actions at the molecular level are actively being refined. We used an integrated genomics approach to profile and characterize the cistrome of TRb, map changes in chromatin accessibility, and capture the transcriptomic changes in response to T3 in normal human thyroid cells. There are significant shifts in TRb genomic occupancy in response to T3, which are associated with differential chromatin accessibility, and differential recruitment of SWI/SNF chromatin remodelers. We further demonstrate selective recruitment of BAF and PBAF SWI/SNF complexes to TRb binding sites, revealing novel differential functions in regulating chromatin accessibility and gene expression. Our findings highlight three distinct modes of TRb interaction with chromatin and coordination of coregulator activity.
2022-04-04 | PXD030403 | Pride
Project description:Metabolomics dataset of serum from T3-treated dams. Related to following publication by Oelkrug et al: "Maternal thyroid hormone receptor beta activation sparks brown fat thermogenesis in the offspring"
2023-01-11 | MSV000091042 | GNPS
Project description:A1-2 cells treated with 100 nM Dexamethasone or ethanol vehicle for 8h. The ability of steroid hormone receptors to initiate a genetic program is tightly regulated by the chromatin environment of the responsive regions. Using the glucocorticoid receptor (GR) as a model factor for transcriptional initiation, we classified chromatin structure through Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE), a technique designed to identify regulatory regions and open chromatin within the genome. We looked at dynamic changes in FAIRE signals prior to and following activation of GR with its ligand, dexamethesone, specifically at regions of receptor interaction. We have found a distribution of GR responsive regions that respond to activation by varying degrees of chromatin modulation. The majority of regions that demonstrate GR interaction also demonstrate increases in FAIRE signal in response to ligand. Most of these GR responsive regions fell within a narrow window of FAIRE signal in the basal chromatin state, suggesting a preferred chromatin structure for GR recruitment. Supporting this notion, global FAIRE-seq data indicated an enrichment of signal surrounding the GR binding site prior to activation. FAIRE signal induction correlated to an increase in nuclease sensitivity and overall FAIRE signal also represented a general accessibility of the chromatin. Further investigation into the requirement of ATPase-dependent chromatin remodeling showed response element specific effects of Brg-1 knockdown. FAIRE induction was universally decreased by Brg-1 depletion, but to varying degrees in a target specific manner. Taken together, these data suggest classes of nuclear receptor response regions that react to activation through different chromatin regulatory events and identify a novel identifier of chromatin structure that classifies the majority of response elements tested.
2012-02-28 | GSE30592 | GEO
Project description:Cancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. In this study, we identify a nuclear hormone receptor (ERα)-protein kinase (ERK5)-cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor-mediated transcription. Using dominant negative and constitutively active forms, as well as small molecule inhibitors of ERK5 and MEK5, we show that hormone activation of estrogen receptor-α determines the nuclear versus cytoplasmic localization of the MAPK family member ERK5, which functions as a coregulator of ERα-gene transcription. Notably, ERK5 works with the actin remodeling protein, CFL1, and upon hormone exposure both became localized to transcription factories in the nucleus, verified by immunofluorescence and proximity ligation assays. Both factors facilitated PAF1 recruitment to the RNA Pol II complex and both ERK5 and CFL1 were required for regulation of gene transcription. By contrast, in cells lacking ERα, ERK5 and CFL1 localized to cytoplasmic membrane regions of high actin remodeling, promoting cell motility and invasion, thereby revealing a mechanism likely to contribute to the generally poorer prognosis of ERα-negative breast cancers. Our study uncovers the dynamic interplay of nuclear receptor-mediated transcription and actin reorganization in phenotypes of breast cancer aggressiveness, and highlights new prognostic biomarkers and suggests novel approaches for developing targeted therapies to moderate cancer aggressiveness. MCF-7 human breast adenocarcinoma cells were tranfected with control, and ERK5 siRNA for 72 hours and treated with 0.1% EtOH (Vehicle) or 10 nM E2 for 24 hours, and cDNA microarray analyses were carried out using Affymetrix [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array. siRNA knock-down, ligand treatment
2014-06-03 | E-GEOD-53394 | biostudies-arrayexpress
Project description:The glucocorticoid receptor (GR) recruits many coregulators via the well characterized AF2 interaction surface in the GR ligand binding domain, but LIM domain coregulator Hic-5 binds to the relatively uncharacterized tau2 activation domain in the hinge region of GR. Requirement of Hic-5 for glucocorticoid-regulated gene expression in U2OS osteosarcoma cells was defined by Hic-5 depletion and global gene expression analysis. Hic-5 depletion had selective and dramatic effects, positive and negative, on both activation and repression of GR target genes. For some hormone-induced genes, Hic-5 facilitated recruitment of the Mediator complex and RNA polymerase II. In contrast, many genes were not regulated by hormone until Hic-5 was depleted. On these genes Hic-5 acted at a very early step of the regulatory process, preventing efficient GR binding on enhancers, chromatin remodeling, and thus preventing glucocorticoid-driven transcriptional regulation. Overall, Hic-5 has selective and diverse roles on GR target genes, functioning as coactivator on some genes and corepressor on others, and either facilitating or opposing the glucocorticoid-driven actions of GR. Hic-5 exhibits multiple mechanisms of action, either regulating GR binding to DNA and chromatin remodeling, or facilitating later steps in transcription complex assembly. We investigate the relationship between GR and Hic5 and identify classes of genes that respond differently when cells are induced with hormone and when Hic5 is knocked down We knock down Hic-5 (TGFB1I1) in U2OS cells using siRNA (siHic5_2) along with nonspecific siRNA (shNS) and assay gene expression changes at 4 different time points of hormone treatment. We also include non-infected control (NI) as a second control at each time point.
2014-03-21 | E-GEOD-46448 | biostudies-arrayexpress
Project description:The glucocorticoid receptor (GR) recruits many coregulators via the well characterized AF2 interaction surface in the GR ligand binding domain, but LIM domain coregulator Hic-5 binds to the relatively uncharacterized tau2 activation domain in the hinge region of GR. Requirement of Hic-5 for glucocorticoid-regulated gene expression in U2OS osteosarcoma cells was defined by Hic-5 depletion and global gene expression analysis. Hic-5 depletion had selective and dramatic effects, positive and negative, on both activation and repression of GR target genes. For some hormone-induced genes, Hic-5 facilitated recruitment of the Mediator complex and RNA polymerase II. In contrast, many genes were not regulated by hormone until Hic-5 was depleted. On these genes Hic-5 acted at a very early step of the regulatory process, preventing efficient GR binding on enhancers, chromatin remodeling, and thus preventing glucocorticoid-driven transcriptional regulation. Overall, Hic-5 has selective and diverse roles on GR target genes, functioning as coactivator on some genes and corepressor on others, and either facilitating or opposing the glucocorticoid-driven actions of GR. Hic-5 exhibits multiple mechanisms of action, either regulating GR binding to DNA and chromatin remodeling, or facilitating later steps in transcription complex assembly. We investigate the relationship between GR and Hic5 and identify classes of genes that respond differently when cells are induced with hormone and when Hic5 is knocked down We knock down Hic-5 (TGFB1I1) in U2OS cells using two different siRNA (siHic5_2 and siHic5_5) along with nonspecific siRNA (shNS) and assay gene expression changes at 4 different time points of hormone treatment. We also include non-infected control (NI) as a second control at each time point.
2016-07-03 | E-GEOD-65401 | biostudies-arrayexpress
Project description:Estrogen receptor M-NM-1 (ER), a member of the nuclear hormone receptor superfamily, regulates transcriptional activity by ligand-dependent recruitment of cofactors which, in turn, locally alter chromatin structure. It is generally believed that co-factor activity at target promoters leads to a more open, transcriptionally permissive chromatin structure, however, these mechanisms remain to be fully established. Peptidylarginine deiminases (PADIs) catalyze the conversion of positively charged arginine and methylarginine residues to neutrally charged citrulline and this activity has been linked to the gene regulation. Here, we found that PADI2 citrullinate H3 Arginine 26 (H3R26) in vitro and, using a specific H3R26 citrulline (H3Cit26) antibody, we demonstrate that H3Cit26 occurs in vivo following 17M-NM-2-estradiol (E2) stimulation and this unique and pronounced global activation of H3Cit26 is ER-dependent. Using a mammalian-based promoter chromosomal array system, we observed that citrullination at H3R26 is robust and co-localizes with ER at decondensed chromatin loci. Additionally, this histone modification is specifically enriched at ER bound regions of target promoters, forming a permissive chromatin environment for gene transactivation. Interestingly, we have shown in a reciprocal way, that either depletion of PADI2 or inhibition of ER not only dramatically abolished E2-induced activation of H3Cit26 on gene promoters but also affect ER recruitment. Collectively, our results demonstrate that citrullination of H3R26 by PADI2 following estrogen stimulation plays a role in ER target gene activation, likely via decondensation of the local chromatin architecture. Two H3Cit26 ChIP-chip biological replicates under vehicle treatment and two H3Cit26 ChIP-chip biological replicates under E2 stimulation from MCF-7 human breast cancer cells are included.
2012-09-04 | E-GEOD-32599 | biostudies-arrayexpress
Project description:Type II nuclear hormone receptors, such as FXR, LXR, and PPAR, which function in glucose and lipid metabolism and serve as drug targets for metabolic diseases, are permanently positioned in the nucleus regardless of the ligand status. Ligand activation of these receptors is thought to occur by co-repressor/co-activator exchange, followed by initiation of transcription. However, recent genome-wide location analysis showed that LXRα and PPARα binding in the liver is largely ligand-dependent. We hypothesized that pioneer factor Foxa2 evicts nucleosomes to enable ligand-dependent receptor binding. We show that chromatin accessibility, FXR binding and LXRα occupancy, and ligand-responsive activation of gene expression by FXR and LXRα require Foxa2. Unexpectedly, Foxa2 occupancy is drastically increased when either receptor, FXR or LXRα, is bound by an agonist. In addition, co-immunoprecipitation experiments demonstrate that Foxa2 interacts with either receptor in a ligand-dependent manner, suggesting that Foxa2 and the receptor bind DNA as an interdependent complex during ligand activation. Furthermore, PPARα binding is induced in Foxa2 mutants treated with FXR and LXR ligands, leading to activation of PPARα targets.
2021-07-12 | GSE149075 | GEO