Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [RNA polymerase ChIP-Seq]

ABSTRACT: Growth factors (GFs) suppression by steroid hormones recurs in embryology and is co-opted in pathology. While studying mammary cell migration, which is stimulated by GFs and antagonized by glucocorticoids (GCs), we found that GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal negative loops. Although no alterations in DNA methylation accompany the transcriptional events instigated by either stimulus, forced demethylation of distal regions broadened the repertoire of inducible genes. Our data indicate that the crosstalk involve transcription factors like p53 and NF-kB, along with reduced pausing (and traveling) of RNA polymerase II (RNAPII) at the promoters (and bodies) of GF-inducible genes. In addition, while GFs hyper-acetylated chromatin at unmethylated promoters and enhancers of genes involved in motility, GCs hypo-acetylated the corresponding regions. In conclusion, stably unmethylated genomic regions that encode feedback regulatory modules and differentially recruit RNAPII and acetylases/deacetylases underlie suppression of growth factor signaling by glucocorticoids.

ORGANISM(S): Homo sapiens

PROVIDER: GSE94062 | GEO | 2017/09/24

SECONDARY ACCESSION(S): PRJNA368705

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [methylation II]

Project description:Growth factors (GFs) suppression by steroid hormones recurs in embryology and is co-opted in pathology. While studying mammary cell migration, which is stimulated by GFs and antagonized by glucocorticoids (GCs), we found that GCs inhibit positive feedback loops activated by GFs and stimulate the reciprocal negative loops. Although no alterations in DNA methylation accompany the transcriptional events instigated by either stimulus, forced demethylation of distal regions broadened the repertoire of inducible genes. Our data indicate that the crosstalk involve transcription factors like p53 and NF-kB, along with reduced pausing (and traveling) of RNA polymerase II (RNAPII) at the promoters (and bodies) of GF-inducible genes. In addition, while GFs hyper-acetylated chromatin at unmethylated promoters and enhancers of genes involved in motility, GCs hypo-acetylated the corresponding regions. In conclusion, stably unmethylated genomic regions that encode feedback regulatory modules and differentially recruit RNAPII and acetylases/deacetylases underlie suppression of growth factor signaling by glucocorticoids.

2017-09-24 | GSE94350 | GEO

Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [GR ChIP-seq]

2017-09-24 | GSE102355 | GEO

Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [IMR90_MCF7_RNA-Seq]

2017-09-24 | GSE94408 | GEO

Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [H3K27Ac ChIP-Seq]

2017-09-24 | GSE94406 | GEO

Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [HCT RNA-Seq]

2017-09-24 | GSE94374 | GEO

Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid hormone [methylation I]

2017-09-24 | GSE94282 | GEO

Yakimchuk2019 - Mathematical modeling of immune modulation by glucocorticoids

Project description:Mathematical modeling of immune modulation by glucocorticoids Konstantin Yakimchuk https://doi.org/10.1016/j.biosystems.2019.104066 Abstract The cellular and molecular mechanisms of immunomodulatory actions of glucocorticoids (GC) remain to be identified. Using our experimental findings, a mathematical model based on a system of ordinary differential equations for characterization of the regulation of anti-tumor immune activity by the both direct and indirect GC effects was generated to study the effects of GC treatment on effector CD8+ T cells, GC-generated tolerogenic dendritic cells (DC), regulatory T cells and the growth of lymphoma cells. In addition, we compared the data from in vivo and in silico experiments. The mathematical simulations indicated that treatment with GCs may suppress anti-tumor immune response in a dose-dependent manner. The model simulations were in line with earlier experimental observations of inhibitory effects of GCs on T and NK cells and DCs. The results of this study might be useful for predicting clinical outcomes in patients receiving GC therapy.

2020-01-06 | MODEL1912170005 | BioModels

Global coupling of R-loops with transcription dynamics modulates early development and survival of Drosophila

Project description:R-loops are involved in many biological processes in cells, yet the regulatory principles for R-loops in vivo and their impact on development remain to be explored. Here, we modified the CUT&Tag strategy to profile R-loops in Drosophila at multiple developmental stages. While high GC content promotes R-loop formation in mammalian cells, it is not required in Drosophila. In contrast, RNAPII abundance on chromatin appears to be a universal inducing factor for R-loop formation in the Drosophila genome, including active promoters and enhancers, and H3K27me3 decorated repressive regions and intergenic repeat sequences. Importantly, such a regulatory relationship is dynamically maintained throughout development and many development-related transcription factors that may regulate RNAPII activation and R-loop dynamics were uncovered. By ablating the elongation factor Spt6, we further showed the global R-loop induction coupled with RNAPII pausing, genome instability, and defects in larvae survival and cuticle development. Overexpression of rnh1 largely reversed the upregulation or downregulation of gene expression depending on gene length, DNA damage, and defects in survival and cuticle development. Altogether, our findings indicate that dynamic R-loop regulation is dictated by RNAP pausing and transcription activity, and plays a feedback role in gene regulation, genome stability maintenance, and Drosophila development.

2024-10-03 | GSE270095 | GEO

Suppression of B-cell development genes is key to glucocorticoid efficacy in treatment of acute lymphoblastic leukemia

Project description:Glucocorticoids (GCs) are a central component of combination chemotherapy for childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). GCs work by activating the glucocorticoid receptor (GR), a ligand induced transcription factor, which in turn regulates genes that induce leukemic cell death. Which GR-regulated genes are required for GC cytotoxicity, the pathways that affect their regulation, and how resistance arises are not well understood. Here we systematically integrate the transcriptional response of B-ALL to GCs with a next-generation shRNA screen to identify GC-regulated “effector” genes that contribute to cell death as well as genes that affect the sensitivity of B-ALL cells to dex. This analysis reveals a pervasive role for GCs in suppression of B-cell development genes that is linked to therapeutic response. Inhibition of PI3Kδ, a lynchpin in the pre-B-cell receptor and IL7R signaling pathways critical to B-cell development, with CAL-101 (idelalisib), interrupts a double-negative feedback loop, enhancing GC-regulated transcription to synergistically kill even highly resistant B-ALL with diverse genetic backgrounds. This work not only identifies numerous opportunities for enhanced lymphoid-specific combination chemotherapy that have the potential to overcome treatment resistance, but is also a valuable resource for understanding GC biology and the mechanistic details of GR-regulated transcription. Please note that the cell lines and primary samples were processed and normalized separately.

2017-02-02 | GSE94302 | GEO

ChIP-MS of Glucocorticoid Receptor in primary mouse macrophages

Project description:Glucocorticoids (GCs) are the most effective anti-inflammatory drugs in current clinical settings, yet their genomic modes of action are poorly understood. GCs bind to the Glucocorticoid Receptor (GR), which acts as a transcription factor to control gene expression in the immune system. Understanding the molecular mechanism that delineates gene repression of pro-inflammatory target genes from gene activation of metabolic genes will help to improve GC therapy and overcome adverse effects.

2021-09-09 | PXD018077 | Pride

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