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RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis [microarray]

ABSTRACT: RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis [microarray]

PROVIDER: PRJNA551438 | ENA |

REPOSITORIES: ENA

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RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis [microarray]

Project description:EWSR1-FLI1 genome reprogramming through remodeling of enhancers is determinant for Ewing sarcoma (ES) tumorigenesis. We describe a non-canonical function of RING1B, a PRC1 subunit highly expressed in primary ES tumors, co-localizing genome wide with EWSR1-FLI1 in active enhancers. While retaining its repressive canonical activity, we find RING1B as necessary for the expression of key EWSR1-FLI1 activated targets like NKX2-2, SOX2 or IGF1 where it mainly exerts a role in promoting oncogene recruitment to enhancers. Knockdown of RING1B is sufficient to impair growth of tumor xenografts and expression of EWSR1-FLI1 induced neomorphic enhancers in vivo. Restoration of RING1B ubiquitin ligase activity by the AURKB inhibitor AZD1152 decreases expression of RING1B/EWSR1-FLI1 common targets. Overall, our findings demonstrate RING1B as a critical modulator of EWSR1-FLI1 induced chromatin remodeling.

2020-10-27 | GSE133425 | GEO

RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis [ChIP-Seq]

2020-10-27 | GSE131286 | GEO

RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis

Project description:RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis

| PRJNA551441 | ENA

RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis [ChIP-Seq]

Project description:RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis [ChIP-Seq]

| PRJNA543121 | ENA

RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis [RNA-seq]

Project description:RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis [RNA-seq]

| PRJNA669990 | ENA

RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis.

Project description:Ewing sarcoma (EwS) is an aggressive tumor that affects adolescents and young adults. EwS is defined by a chromosomal translocation, EWSR1-FLI1 being the most common, that causes genome reprogramming through remodeling of enhancers. Here, we describe an unexpected function of RING1B, which is highly expressed in EwS. While retaining its repressive activity at Polycomb developmental regulated genes, RING1B colocalizes with EWSR1-FLI1 at active enhancers. We demonstrate that RING1B is necessary for the expression of key EWSR1-FLI1 targets by facilitating oncogene recruitment to their enhancers. Knockdown of RING1B impairs growth of tumor xenografts and expression of genes regulated by EWSR1-FLI1 bound enhancers. Pharmacological inhibition of AURKB with AZD1152 increases H2Aub levels causing down-regulation of RING1B/EWSR1-FLI1 common targets. Our findings demonstrate that RING1B is a critical modulator of EWSR1-FLI1-induced chromatin remodeling, and its inhibition is a potential therapeutic strategy for the treatment of these tumors.

| S-EPMC7608835 | biostudies-literature

RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis [RNA-seq]

Project description:Analysis of differential expression profiles of tumors wild-type and RING1B knock-down

2020-10-27 | GSE159525 | GEO

Endogenous degron alleles enable tunable control of EWSR1-FLI1 oncoprotein expression

Project description:Pediatric malignancies frequently harbor chromosomal translocations that induce expression of fusion oncoproteins. The EWSR1-FLI1 fusion oncoprotein acts as a neomorphic transcription factor and is the dominant genetic driver of Ewing’s sarcoma. However, interrogation of the mechanisms by which EWSR1-FLI1 drives tumorigenesis has been limited by a lack of model systems to precisely and selectively control its expression in patient-derived cell lines and xenografts. Here, we report the generation of a panel of patient-derived EWS cell lines in which inducible protein degrons have been engineered into the endogenous EWSR1-FLI1 locus. These systems enable precise control of EWSR1-FLI1 expression and the timing of oncoprotein depletion. We establish that complete suppression of EWSR1-FLI1 leads to a reversible cell cycle arrest at the G1-S phase transition, and we identify a core set of transcripts downstream of EWSR1-FLI1 across multiple cell lines and degron systems. Additionally, depletion of EWSR1-FLI1 using this system potently suppresses tumor growth in xenograft models validating efforts to directly target EWSR1-FLI1 in Ewing’s sarcoma.

2025-01-20 | GSE270570 | GEO

RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-10-27 | GSE133427 | GEO

Gene expression profiling of human Ewing sarcoma cells after knockdown of EGR2 or EWSR1-FLI1.

Project description:To get insight in the functional role of EGR2 for Ewing sarcoma, we performed a transcriptional profiling of Ewing sarcoma cells after knockdown of EGR2 and compared the resulting transcriptional signature with that of EWSR1-FLI1-silenced Ewing sarcoma cells. In accordance with the strong EGR2-induction by EWSR1-FLI1, both genes highly significantly overlap in their transcriptional signatures. Gene-set enrichment analyses (GSEA) and DAVID (Database for Annotation, Visualisation and Integrated Discovery) gene ontology analyses indicated a strong impact of EGR2 on cholesterol and lipid biosynthesis resembling its function in orchestrating lipid metabolism of myelinating Schwann cells. A673 and SK-N-MC Ewing sarcoma cells were transfected with specific siRNAs directed against EGR2 or EWSR1-FLI1 or non-targeting control siRNA. 48 h thereafter RNA was harvested and processed for microarray analysis.

2015-07-26 | E-GEOD-62090 | biostudies-arrayexpress

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