Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE193988 | GEO | 2022/05/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression.

Project description:The rapid transcriptional response to the transcription factor, glucocorticoid receptor (GR), including gene activation or repression, is mediated by the spatial association of genes with multiple GR binding sites (GBSs) over large genomic distances. However, only a minority of the GBSs have independent GR-mediated activating capacity, and GBSs with independent repressive activity were rarely reported. To understand the positive and negative effects of GR we mapped the regulatory environment of its gene targets. We show that the chromatin interaction networks of GR-activated and repressed genes are spatially separated and vary in the features and configuration of their GBS and other non-GBS regulatory elements. The convergence of the KLF4 pathway in GR-activated domains and the STAT6 pathway in GR-repressed domains, impose opposite transcriptional effects to GR, independent of hormone application. Moreover, the ROR and Rev-erb transcription factors serve as positive and negative regulators, respectively, of GR-mediated gene activation. We found that the spatial crosstalk between GBSs and non-GBSs provides a physical platform for sequestering the Ep300 co-activator from non-GR regulatory loci in both GR-activated and -repressed gene compartments. While this allows rapid gene repression, Ep300 recruitment to GBSs is productive specifically in the activated compartments, thus providing the basis for gene induction.

| S-EPMC9262608 | biostudies-literature

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

Project description:The transcription factor glucocorticoid receptor (GR) is a key mediator of stress response and a broad range of physiological processes. How can GR rapidly activate the expression of some genes while repress others, remains an open question due to the challenge to associate GR binding sites (GBSs) to their distant gene targets. Mapping the 3D scope of GR-responsive promoters using high-resolution 4C-seq unravelled spatial separation between chromatin interaction networks of GR-activated and repressed genes. The spatial compartments of GR-activated and GR-repressed genes vary in the types and configuration of their residing regulatory elements. GR binding to chromatin sequester the co-activator Ep300 from non-GR regulatory loci in GR-activated and repressed gene compartments. While this allows rapid gene repression, effective Ep300 recruitment to GR binding sites positioned within the activated compartments provide the basis for gene induction. Moreover, focused analysis on GBS together with other regulatory loci that cluster in the GR activated compartments identifies ROR, Rev-erb, and Klf4 transcription factors as co-regulators for GR-mediated gene expression. Thus spatial crosstalk between various regulatory loci in GR-responsive compartments provides the basis for precise transcriptional response

2022-05-29 | GSE193986 | GEO

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

2020-10-31 | GSE106209 | GEO

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

2022-05-29 | GSE193987 | GEO

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

Project description:Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

| PRJNA798694 | ENA

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

Project description:Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

| PRJNA798686 | ENA

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

Project description:Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

| PRJNA798695 | ENA

Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

Project description:Ep300 sequestration to functionally distinct glucocorticoid receptor binding loci underlie rapid gene activation and repression

| PRJNA415926 | ENA

Glucocorticoid Receptor Binding Induces Rapid and Prolonged Large-Scale Chromatin Decompaction at Multiple Target Loci.

Project description:Glucocorticoids act by binding to the glucocorticoid receptor (GR), which binds to specific motifs within enhancers of target genes to activate transcription. Previous studies have suggested that GRs can promote interactions between gene promoters and distal elements within target loci. In contrast, we demonstrate here that glucocorticoid addition to mouse bone-marrow-derived macrophages produces very rapid chromatin unfolding detectable by fluorescence in situ hybridization (FISH) at loci associated with GR binding. Rapid chromatin decompaction was generally not dependent on transcription at those loci that are known to be inducible in both mouse and human macrophages and was sustained for up to 5 days following ligand removal. Chromatin decompaction was not dependent upon persistent GR binding, which decayed fully after 24 hr. We suggest that sustained large-scale chromatin reorganization forms an important part of the response to glucocorticoid and might contribute to glucocorticoid sensitivity and resistance.

| S-EPMC5745231 | biostudies-literature

Cryptochromes mediate rhythmic repression of the glucocorticoid receptor.

Project description:Mammalian metabolism is highly circadian and major hormonal circuits involving nuclear hormone receptors display interlinked diurnal cycling. However, mechanisms that logically explain the coordination of nuclear hormone receptors and the clock are poorly understood. Here we show that two circadian co-regulators, cryptochromes 1 and 2, interact with the glucocorticoid receptor in a ligand-dependent fashion and globally alter the transcriptional response to glucocorticoids in mouse embryonic fibroblasts: cryptochrome deficiency vastly decreases gene repression and approximately doubles the number of dexamethasone-induced genes, suggesting that cryptochromes broadly oppose glucocorticoid receptor activation and promote repression. In mice, genetic loss of cryptochrome 1 and/or 2 results in glucose intolerance and constitutively high levels of circulating corticosterone, suggesting reduced suppression of the hypothalamic-pituitary-adrenal axis coupled with increased glucocorticoid transactivation in the liver. Genomically, cryptochromes 1 and 2 associate with a glucocorticoid response element in the phosphoenolpyruvate carboxykinase 1 promoter in a hormone-dependent manner, and dexamethasone-induced transcription of the phosphoenolpyruvate carboxykinase 1 gene was strikingly increased in cryptochrome-deficient livers. These results reveal a specific mechanism through which cryptochromes couple the activity of clock and receptor target genes to complex genomic circuits underpinning normal metabolic homeostasis.

| S-EPMC3245818 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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