Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide nucleosome dynamics in glucocorticoid-treated acute lymphoblastic leukemia cell line, RS4;11

ABSTRACT: Precise nucleosome positioning is an increasingly recognized feature of promoters and enhancers, reflecting complex contributions of DNA sequence, nucleosome positioning, histone modification and transcription factor binding to enhancer activity and regulation of gene expression. Changes in nucleosome position and occupancy, histone variants and modifications, and chromatin remodeling are also critical elements of dynamic transcriptional regulation, but poorly understood at enhancers. We investigated glucocorticoid receptor-associated (GR) nucleosome dynamics at enhancers in acute lymphoblastic leukemia. For the first time, we demonstrate functionally distinct modes of nucleosome remodeling upon chromatin binding by GR, which we term central, non-central, phased, and minimal. Central and non-central remodeling reflect nucleosome eviction by GR and cofactors, respectively. Phased remodeling involves nucleosome repositioning and is associated with rapidly activated enhancers and induction of gene expression. Minimal remodeling sites initially have low levels of enhancerassociated histone modification, but the majority of these regions gain H3K4me2 or H3K27Ac to become de novo enhancers. Minimal remodeling regions are associated with gene ontologies specific to decreased B cell number and mTOR inhibition and may make unique contributions to glucocorticoid-induced leukemia cell death. Our findings form a novel framework for understanding the dynamic interplay between transcription factor binding, nucleosome remodeling, enhancer function, and gene expression in the leukemia response to glucocorticoids.

ORGANISM(S): Homo sapiens

PROVIDER: GSE71616 | GEO | 2015/10/01

SECONDARY ACCESSION(S): PRJNA291622

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expression data from glucocorticoid-treated acute lymphoblastic leukemia cell line, RS4;11

Project description:Precise nucleosome positioning is an increasingly recognized feature of promoters and enhancers, reflecting complex contributions of DNA sequence, nucleosome positioning, histone modification and transcription factor binding to enhancer activity and regulation of gene expression. Changes in nucleosome position and occupancy, histone variants and modifications, and chromatin remodeling are also critical elements of dynamic transcriptional regulation, but poorly understood at enhancers. We investigated glucocorticoid receptor-associated (GR) nucleosome dynamics at enhancers in acute lymphoblastic leukemia. For the first time, we demonstrate functionally distinct modes of nucleosome remodeling upon chromatin binding by GR, which we term central, non-central, phased, and minimal. Central and non-central remodeling reflect nucleosome eviction by GR and cofactors, respectively. Phased remodeling involves nucleosome repositioning and is associated with rapidly activated enhancers and induction of gene expression. Minimal remodeling sites initially have low levels of enhancerassociated histone modification, but the majority of these regions gain H3K4me2 or H3K27Ac to become de novo enhancers. Minimal remodeling regions are associated with gene ontologies specific to decreased B cell number and mTOR inhibition and may make unique contributions to glucocorticoid-induced leukemia cell death. Our findings form a novel framework for understanding the dynamic interplay between transcription factor binding, nucleosome remodeling, enhancer function, and gene expression in the leukemia response to glucocorticoids. We used microarrays to measure changes in gene expression following treatment of cells with dexamethasone for 0, 8, or 24 hours.

2015-10-01 | GSE71615 | GEO

Conventional and pioneer modes of glucocorticoid receptor interaction with enhancer chromatin in vivo

Project description:Glucocorticoid hormone plays a major role in metabolism and many related diseases. The hormone-bound glucocorticoid receptor (GR) binds to a specific set of enhancers in different cell types, resulting in unique patterns of gene expression. GR-responsive enhancers have an accessible chromatin structure prior to hormone treatment (“pre-programmed”), whereas unresponsive enhancers specific to other cell types are inaccessible and inactive. Here we have addressed the role of chromatin structure in cell-specific GR-enhancer programming by precise mapping of nucleosome positions in mouse adenocarcinoma cells. We show that, before hormone treatment, some pre-programmed GR-enhancers are nucleosome-depleted, associated with the Brg1 chromatin remodeler and flanked by nucleosomes exchanging histones H2A.Z and H2A. However, most pre-programmed GR-enhancers are assembled into a nucleosome that exchanges H2A.Z and H2A, with little or no Brg1. After hormone treatment, nucleosomes at both types of pre-programmed GR-enhancer shift apart, coinciding with increased levels of Brg1, and continue to exchange H2A.Z and H2A. Hormone removal rapidly reverses these nucleosome shifts. In contrast, inactive GR-enhancers are nucleosomal, lack Brg1, do not exchange H2A.Z or H2A and do not respond to hormone. Thus, pre-programmed GR-enhancers are marked by a dynamic, mutable chromatin structure characterized by high levels of H2A.Z exchange. We propose that nucleosome-depleted GR-enhancers result from the binding of other transcription factors together with Brg1 to assist loading of GR after hormone treatment. At nucleosomal enhancers, GR binding may be directly facilitated by increased transient exposure of enhancer DNA associated with H2A.Z exchange.

2017-11-06 | GSE92505 | GEO

SUMOylation regulates chromatin protein network and accessibility at glucocorticoid receptor-binding sites

Project description:Glucocorticoid receptor (GR) is an essential transcription factor (TF), controlling metabolism, development and immune responses. SUMOylation regulates chromatin occupancy and target gene expression of GR in a locus-selective manner, but the mechanism of regulation has remained elusive. Here, we show using selective isolation of chromatin-associated proteins that the protein network around chromatin-bound GR is affected by SUMOylation, with several nuclear receptor coregulators and chromatin modifiers being more avidly associated with SUMOylation-deficient than SUMOylation competent GR. This difference is reflected in our chromatin accessibility and gene expression data, showing that the SUMOylation-deficient GR is more potent in opening chromatin at glucocorticoid-regulated enhancers and inducing expression of their target loci. Our results thus show that SUMOylation determines GR specificity by regulating the chromatin protein network and accessibility at GR-driven enhancers. We speculate that a similar mechanism is utilized by many other SUMOylated TFs.

2021-09-08 | PXD015183 | Pride

Selective enhancement and repression of glucocorticoid receptor signaling by coregulator Hic-5

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

Selective coregulator function for different steroid receptors and restriction of steroid receptor chromatin occupancy by Hic-5 (GRÎ³)

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

Selective coregulator function for different steroid receptors and restriction of steroid receptor chromatin occupancy by Hic-5 (GRγ)

2016-01-01 | GSE65401 | GEO

Selective enhancement and repression of glucocorticoid receptor signaling by coregulator Hic-5

2014-03-21 | GSE46448 | GEO

Conventional and pioneer modes of glucocorticoid receptor interaction with enhancer chromatin in vivo

Project description:Here we show how chromatin structure is involved in glucocorticoid receptor (GR) binding in a mouse mammary cell line. We show that GR binds to accessible chromatin sites that are either nucleosome-free or contain a nucleosome.

2017-11-06 | GSE94562 | GEO

Glucocorticoid inducton of DDIT4 transcription

Project description:The hormone stimulated Glucocorticoid Receptor (GR) modulates transcription by interacting with thousands of enhancers and GR binding sites (GBSs) throughout the genome. Here, we examined the effects of GR binding on enhancer dynamics and interrogated the contributions of individual GBSs to the hormone response. Hormone treatment resulted in genome-wide reorganization of the enhancer landscape in breast cancer cells. Upstream of the DDIT4 oncogene, GR bound to four sites constituting a hormone-dependent super enhancer. Three GBSs were required as hormone-dependent enhancers that differentially promoted histone acetylation and transcription frequency and burst size. Conversely, the fourth site suppressed transcription and hormone treatment alleviated this suppression. GR binding within the super enhancer promoted a loop-switching mechanism that allowed interaction of the DDIT4 TSS with the active GBSs. The unique functions of each GR binding site contributed to hormone-induced transcriptional heterogeneity and demonstrate the potential for targeted modulation of oncogene expression.

2022-01-24 | GSE173798 | GEO

ChIP-MS for GR in liver from wild type and E47 mutant mice

Project description:Glucocorticoids (GCs) are widely prescribed effective drugs, but their clinical use is compromised by severe side effects including hyperglycemia, hyperlipidemia and obesity. They bind to the Glucocorticoid Receptor (GR), which acts as a ligand-gated transcription factor. The transcriptional activation of metabolic genes by GR is thought to underlie these undesired adverse effects. Using mouse genetics, ChIP-Seq, RNA-Seq and ChIP-MS, we found that the bHLH transcription factor E47 is required for the regulation of hepatic glucose and lipid metabolism by GR in vivo, and that loss of E47 prevents the development of hyperglycemia and hepatic steatosis in response to GCs. Here we show that E47 and GR co-occupy metabolic promoters and enhancers. E47 is needed for the efficient binding of GR to chromatin and for the adequate recruitment of coregulators such as Mediator. Taken together, our results illustrate how GR and E47 regulate hepatic metabolism, and how inhibition of E47 might provide an entry point for novel GC therapies with reduced side effect profiles. These ChIP-MS data sets show IPs for GR in both wildtype and E47 mutant mouse livers treated with the synthetic glucocorticoid Dexamethasone.

2018-11-22 | PXD010157 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data