Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scATAC-seq]

ABSTRACT: Performed scATAC-seq in 3 timepoints of an autochthonous mouse model. A proliferative population is characterized by an ERG-specific chromatin state enriched for NFkB, AP-1, STAT and NFAT binding, with implications for TF cooperativity. ERG is enriched in a small stem-like population implicates the chromatin context of these cells as a critical variable for unmasking its oncogenic activity.

ORGANISM(S): Mus musculus

PROVIDER: GSE258962 | GEO | 2025/04/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scRNA-seq]

Project description:Performed scRNA-seq of an autochthonous mouse model at an early stage of disease initiation. Despite broad expression of ERG in all prostate epithelial cells, proliferation was enriched in a small, stem-like population of cells with mixed-luminal basal identity (intermediate cells).

2025-04-07 | GSE257543 | GEO

The transcriptional network of wild type ERG and ERG mutant at K362

Project description:We have identified a specific site in the ERG protein that undergoes post-transcriptional modification. We have mutated this site and generated stably expressing LNCaP cell lines. In this study we evaluated the transcriptional profile induced by ERG in LNCaP stably expressing ERG wild type , ERG mutant or empty vector (EV).

2018-07-31 | GSE71329 | GEO

High ERG expression in human HSPCs promotes progenitor but not stem cell proliferation and molecular signatures that are enriched in high ERG leukemia.

Project description:ERG is an Ets-transcription factor required for normal blood stem cell development. High ERG expression in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL) is associated with a stem cell signature and poor prognosis. In murine over-expression models, human ERG is a potent oncogene that induces both T-ALL and AML. However the functional and molecular consequences of high ERG expression in normal hematopoietic stem/progenitors (HSPCs), and how this contributes to leukemia development, are unknown. Here we show that retroviral transduction of ERG into human CD34+ cells and maintenance of ERG at levels present in high ERG AML results in altered myeloid and T cell differentiation and an increase in the self-renewal capacity of transduced progenitors but not the more primitive stem cell compartment. Integrated analysis of genome-wide expression in high ERG CD34+ and ERG binding profiles in HSPCs revealed that these functional characteristics were accompanied by an expression signature that was enriched in normal HSCs, high ERG AMLs, early T-cell precursor (ETP)-ALLs and leukemic stem cell signatures associated with poor clinical outcome. The proliferative advantage of high ERG progenitors may provide a cellular context for the acquisition and propagation of mutations that contribute to the pathogenesis of leukaemia. RNA sequencing in ERG overexpressing human CD34+ cells

2014-10-31 | E-GEOD-53665 | biostudies-arrayexpress

ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning

Project description:Precise vascular patterning is critical for normal growth and development. The ERG transcription factor drives Delta like ligand 4 (DLL4)/Notch signalling and is thought to act as pivotal regulators of endothelial cell (EC) dynamics and developmental angiogenesis. However, molecular regulation of ERG activity remains obscure. Using a series of EC specific Focal Adhesion Kinase (FAK)-knockout (KO) and point-mutant FAK-knockin mice, we show that loss of ECFAK, its kinase activity or phosphorylation at FAK-Y397, but not FAK-Y861, reduces ERG and DLL4 expression levels together with concomitant aberrations in vascular patterning. Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins identified that endothelial nuclear-FAK interacts with the de-ubiquitinase USP9x and the ubiquitin ligase TRIM25 enzymes. Further in silico analysis corroborates that ERG interacts with USP9x and TRIM25. Moreover, ERG levels are reduced in FAKKO ECs via a ubiquitin-mediated post-translational modification programme involving USP9x and TRIM25. Re-expression of ERG in vivo and in vitro rescues the aberrant vessel sprouting defects observed in the absence of ECFAK. Our findings identify ECFAK as a regulator of retinal vascular patterning by controlling ERG protein degradation via TRIM25/USP9x.

2022-07-05 | PXD033447 | Pride

Methylation-induced conformational switch enables ERG oncogenic activation and prostate cancer progression

Project description:The TMPRSS2-ERG gene fusion is the most frequent alteration observed in human prostate cancer but its role in disease progression is still debated. In this study, we uncovered a novel molecular mechanism promoting progression in ERG-fusion positive prostate cancer. We show that ERG is methylated by Enhancer of zest homolog 2 (EZH2) at a specific lysine residue (K362) located within the internal auto-inhibitory domain. Mechanistically, K362 mono- methylation prevents intra-domain interactions, favors DNA binding and promotes ERG transcriptional and oncogenic activity in cellular and mouse models. Consistently with the involvement in ERG oncogenesis, we found that K362 methylation was associated with disease progression in ERG transgenic mouse models and was enhanced by PTEN deficiency and AKT activation, which promoted EZH2 substrate switching from histone H3K27 to ERG. Conversely, EZH2 inhibition blocked ERG methylation along with ERG-induced transcriptional and phenotypic reprogramming in cell cultures and ERG/PTEN mice. We found that ERG and EZH2 co-occupy several genomic regions forming prevalently co-activating complexes. The network of ERG/EZH2 co-regulated target genes was enriched of functionally aggressive features and was associated preferentially with concomitant ERG gain and PTEN loss, castration-resistance and adverse clinical outcome in prostate cancer patients. Collectively, these findings identify ERG methylation as a novel post-translational modification sustaining disease progression in ERG-positive prostate cancers. Our data also provide an attractive rationale for developing molecularly targeted therapeutics to antagonize ERG oncogenic activity.

2021-04-16 | GSE159471 | GEO

Staphylococcal Nuclease and Tudor Domain Containing protein SND1 interacts with ERG and plays a critical role in prostate cancer in vivo

Project description:SND1 and its partner MTDH promote cancer and therapeutic resistance; however, the mechanisms responsible for their function and potential cooperation with other oncogenes are not completely understood. We report here that oncoprotein ERG binds to the SND1/MTDH protein complex via the Tudor domain of SND1. ERG is an ETS-domain transcriptional factor, which is recombined and overexpressed in approximately half of human prostate cancers. siRNA-mediated knockdowns and CRISPR-Cas9-mediated knockout of SND1 in human prostate epithelium cell lines revealed a critical role of SND1 in proliferation of ERG-overexpressing prostate epithelial cells. Transcriptional analysis of ERG-positive human prostate cancer cells demonstrated significant overlap between genes regulated by ERG and SND1. Mechanistically, we found that ERG promoted nuclear localization of SND1/MTDH. Significantly, forced nuclear localization of SND1 by addition of exogenous nuclear localization sequences (NLS) prominently increased its growth promoting function irrespective of the status of ERG expression. To determine if SND1 is necessary for prostate cancer tumorigenesis in vivo, we generated mice with prostate-epithelium-specific deletion of Snd1. We found that inactivation of Snd1 did not impact normal prostate gland homeostasis. However, prostate epithelium-specific deletion of Snd1 in autochthonous mouse model of prostate cancer (PB-Cre/ERG/PTENflox/flox mice) showed greatly reduced invasive cancer growth and tumor burden. Moreover, gene expression analysis revealed a significant overlap between in vivo prostate transcriptional signatures of ERG and Snd1. We conclude that SND1 plays a critical role in prostate tumorigenesis and targeting SND1 may represent a potential therapeutic target in prostate cancer.

2023-09-11 | GSE212840 | GEO

Staphylococcal Nuclease and Tudor Domain Containing protein SND1 interacts with ERG and plays a critical role in prostate cancer in vivo

Project description:ERG is a transcriptional factor, which is recombined with promoter of TMPRSS2 and prominently overexpressed in half of human prostate cancers. The mechanisms of ERG-mediated oncogenesis are not completely understood. We performed an unbiased Mass Spectrometry screen for ERG-binding proteins and found that ERG binds to MTDH/SND1 protein complex in prostate cancer cells. We determined that ERG binds to the SND1/MTDH protein complex via SND1 and this interaction plays a critical role in ERG-mediated cancer.

2023-03-22 | PXD036882 | Pride

Microarray expression analysis of wild type and Erg knockdown bone marrow hematopoietic stem and progenitor cells

Project description:Erg is an ETS family transcription factor frequently overexpressed in human leukemias and has been implicated as a key regulator of hematopoietic stem cells (HSCs). However how Erg controls normal hematopoiesis, particularly at the stem cell level, remains poorly understood. Using homologous recombination, we generated an Erg knockdown allele (Ergkd) in which Erg expression can be restored upon Cre-mediated excision of a Stopper cassette. In Ergkd/+ mice, ~40% reduction in Erg dosage perturbed both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors. By genetic mosaic analysis, we found Erg-restored HSPCs outcompeted Ergkd/+ HSPCs for contributing to adult hematopoiesis in vivo. Intriguingly, HSC differentiation also appeared attenuated, leading to accumulation of long-term HSCs in the mutant LSK population. Accordingly, microarray analysis of Erg-restored and Ergkd/+ HSPCs from the same animal revealed enrichment of stem cell-related pathways in Ergkd/+ HSPCs. Overall, reduced Erg dosage perturbs hematopoiesis by reducing HSC numbers and impairing HSC differentiation, possibly via two Erg targets, Jun and Myc.

2017-06-20 | GSE48600 | GEO

ERG-mediated coregulator complex formation maintains androgen receptor signaling in prostate cancer [ERG ChIP]

Project description:We report the effects of ERG on prostate tumorigenesis, ERG-mediated oncogene addiction, and downstream AR signaling pathways. We determined that ERG facilitates AR-signaling and mediates transformation of prostate cells by maintaining coregulator complex formation at AR-bound sites across the genome.

2020-09-04 | GSE157406 | GEO

The transcription factor ERG regulates super-enhancers in endothelial cells [ERG siRNA]

Project description:We provide the functional and epigenomic evidence for ERG binding to super-enhancers in HUVEC and further show that loss of ERG results in inhibition of specific endothelial super-enhancers and associated target genes.

2019-03-22 | GSE124892 | GEO

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