ChIP-seq analysis of RARB enrichment in SUIT2 pancreatic cancer cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 500
ORGANISM(S): Homo sapiens
SUBMITTER: Stephen Thorpe
PROVIDER: E-MTAB-12792 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Retinoic Acid Receptors (RARs) as a functional heterodimer with Retinoid X Receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR-RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insight for the recognition of DR5 and DR0 elements by RXR-RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structure of RXR-RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, on DR0 the two molecules bound non-cooperatively on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR-RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding mode between DR0 and DR5 were observed leading to differences in the conformation and structural dynamics of the multi-domain RXR-RAR DNA complex. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR-RAR heterodimers.
2021-02-10 | PXD018172 | Pride
Project description:Percellome analysis of whole Xenopus embryos at developmental stage 18 Xenopus embryos were treated with TTNPB (RAR-agonist), AGN193109 (RAR-antagonist), or Control Vehicle at Nieuwkoop and Faber Stage 7. Embryos were collected at stage 18, followed by RNA extraction, hybridization on Affymetrix microarrays, and Percellome analysis.
2014-05-06 | E-GEOD-57352 | biostudies-arrayexpress
Project description:To elucidate the specific molecular signals associated with the activation or blockade of CB1 and CB2 receptors in this glial cell, mass spectrometry-based proteomics and in silico biology tools were used to determine which signaling pathways and molecular mechanisms are triggered in a human oligodendrocytic cell line (MO3.13) by several pharmacological stimuli: the phytocannabinoid cannabidiol (CBD); CB1 and CB2 agonists WIN55,212-2, ACEA, and HU308; CB1 and CB2 antagonists AM251 and AM630; and endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG).
2022-06-09 | PXD031923 | Pride
Project description:Retinoic acid (RA) triggers physiological processes by activating heterodimeric transcription factors comprising retinoic acid (RARa,b,g) and retinoid X (RXRa,b,g) receptors. How a single signal induces highly complex temporally controlled networks that ultimately orchestrate physiological processes is unclear. Using an RA-inducible differentiation model we defined the temporal changes in the genome-wide binding patterns of RARg and RXRa and correlated them with transcription regulation. Unexpectedly, both receptors displayed a highly dynamic binding, with different RXRa heterodimers targeting identical loci. Comparison of RARg and RXRa co-binding at RA-regulated genes identified putative RXRa-RARg target genes that were validated with subtype-selective agonists. Gene regulatory decisions during differentiation were inferred from transcription factor target gene information and temporal gene expression. This analysis revealed 6 distinct co-expression paths of which RXRa-RARg is associated with transcription activation, while Sox2 and Egr1 were predicted to regulate repression. Finally, RXRa-RARg regulatory networks were reconstructed through integration of functional co-citations. Our analysis provides a dynamic view of RA signalling during cell differentiation, reveals RA heterodimer dynamics and promiscuity, and predicts decisions that diversify the RA signal into distinct gene-regulatory programs. Transcriptional activity in F9 cells treated with different retinoic acid receptor (RAR) agonists; like all-trans retinoic acid (ATRA), BMS961 (RARg-specific), BMS753 (RARa-specific) or BMS641(RARb-specific); has been evaluated at different time-points (2, 6, 24, 48h) and compared with that found under Ethanol-vehicle treatment conditions (48h treatment).
2011-10-10 | E-GEOD-30537 | biostudies-arrayexpress
Project description:Inactivation of RAR-b, which has been reported as a tumor suppressing gene by numerous studies, results in protective effect against the tumorigenesis induced by activated ErbB2. Moreover, tissue recombination indicates that the RAR-b deficient-microenvironment, rather than the RAR-b status of mammary epithelial cells, plays a key-determining role in the initiation and progression of the mammary carcinoma. Ablation of RAR-b extensively modulates the remodeling of stroma during tumor progression through suppressing the activation and transdifferetiation of myofibroblasts. RNA microarray has been employed to identify the gene expression signature in the mammary stroma of our RAR-b null animals. We want to find out the underlining mechanism of the protective effects resulted from Rarb abliton.
2010-12-18 | GSE19925 | GEO
Project description:Retinoic Acid Receptors (RARs) bind RA-response elements in regulatory regions of their target genes. While canonical RAREs comprise direct repeats of the consensus 5’-RGKTCA-3’ sequence separated by 1, 2 or 5 nucleotides (DR1, DR2, DR5), we show that shortly after RA treatement of mouse embryoid bodies or F9 cells, RARs occupy a large repertoire of DR0, DR2, DR5, DR8 and IR0 elements. In vitro, RAR-RXR bind these non-canonical spacings with comparable affinities to DR2 and DR5. Most DR8 elements comprise three half sites with DR2 and DR0 spacings. This specific half site organisation constitutes a previously unrecognised, but frequent signature of RAR binding elements and acts as an RARE. At later stages of embryoid body differentiation, RARs relocalise to a restricted repertoire of sites comprising predominantly DR5 elements. Differentiation thus involves genomic relocalisation of RARs, and a switch from DR0 and DR8 at early times to DR5 at later stages. Examination of genomic localisation of RAR in differentiating embryoid bodies.
2012-06-15 | E-GEOD-35599 | biostudies-arrayexpress
Project description:Inactivation of RAR-b, which has been reported as a tumor suppressing gene by numerous studies, results in protective effect against the tumorigenesis induced by activated ErbB2. Moreover, tissue recombination indicates that the RAR-b deficient-microenvironment, rather than the RAR-b status of mammary epithelial cells, plays a key-determining role in the initiation and progression of the mammary carcinoma. Ablation of RAR-b extensively modulates the remodeling of stroma during tumor progression through suppressing the activation and transdifferetiation of myofibroblasts. RNA microarray has been employed to identify the gene expression signature in the mammary stroma of our RAR-b null animals. We want to find out the underlining mechanism of the protective effects resulted from Rarb abliton. A global gene expression profile of mouse mammary stroma was obtained on total RNA from the cleared mammary fat pads (stroma) of both RAR-b KO (n=3) and their wild type (n=3) littermates at the age of four weeks.
2010-12-18 | E-GEOD-19925 | biostudies-arrayexpress
Project description:Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists have demonstrated therapeutic properties for several brain disorders, including alcohol dependence. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated and little is known about their effects in the brain. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar and fenofibrate decreased ethanol consumption in male C57BL/6J mice while bezafibrate did not. Hypothesizing that fenofibrate and tesaglitazar are causing brain gene expression changes that precipitate the reduction in ethanol drinking, we gave daily oral injections of fenofibrate, tesaglitazar and bezafibrate to mice for eight consecutive days and collected liver, prefrontal cortex and amygdala 24 hours after last injection. RNA was isolated and purified using MagMAX-96 Total RNA Isolation Kit. Biotinylated, amplified cRNA was generated using Illumina TotalPrep RNA Amplification Kit and hybridized to Illumina MouseWG-6 v2.0 Expression microarrays. Mice were divided into four groups (N=10 per group): fenofibrate, tesaglitazar, bezafibrate and saline. See summary and protocols for details.
2015-04-14 | E-GEOD-67796 | biostudies-arrayexpress
Project description:The aim of this study was to determine the in vitro effects of peroxisome proliferator-activated receptor-beta/delta (PPARβ/δ) ligands on the transcriptomic profile of the LPS-stimulated pig CL in the mid-luteal phase of the estrous cycle using RNA-seq technology. The CL slices were incubated in the presence of LPS or in combination with LPS and the PPARβ/δ agonist-GW0724 (1 μmol/L or 10 μmol/L) or the antagonist-GSK3787 (25 μmol/L). We identified 117 differentially expressed genes after treatment with LPS; 102 and 97 differentially expressed genes after treatment respectively with the PPARβ/δ agonist at a concentration of 1 μmol/L or 10 μmol/L, as well as 88-after treatment with the PPARβ/δ antagonist
2022-09-01 | E-MTAB-12027 | biostudies-arrayexpress
Project description:Among its many roles in development, retinoic acid determines the anterior-posterior identity of differentiating motor neurons by activating Retinoic Acid Receptor (RAR)-mediated transcription. RAR is thought to bind the genome constitutively, and only induce transcription in the presence of the retinoid ligand. However, little is known about where RAR binds to the genome or how it selects target sites. We tested the constitutive RAR binding model using the retinoic acid-driven differentiation of mouse embryonic stem cells into differentiated motor neurons. We find that retinoic acid treatment results in widespread changes in RAR genomic binding, including novel binding to genes directly responsible for anterior-posterior specification, as well as the subsequent recruitment of the basal polymerase machinery. Finally, we discovered that the binding of transcription factors at the embryonic stem cell stage can accurately predict where in the genome RAR binds after initial differentiation. We have characterized a ligand-dependent shift in RAR genomic occupancy at the initiation of neurogenesis. Our data also suggests that enhancers active in pluripotent embryonic stem cells may be preselecting regions that will be activated by RAR during neuronal differentiation. The differentiation of ventral motor neurons is induced by treating embryonic stem cell cultures with retinoic acid. Here, ChIP-seq is used to profile the genome-wide occupancy of RAR isofroms both immediately prior to and during exposure of the cells to retinoic acid. ChIP-seq is also used to profile the genomic occupancy of Pol2 with phosphorylated serine 5 (Pol2-S5P) and phosphorylated serine 2 (Pol2-S2P) after exposure to retinoic acid.
2010-12-10 | E-GEOD-19409 | biostudies-arrayexpress