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

2020-10-27 | GSE159525 | GEO

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 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

Knowk-down of EWSR1-FLI1 in Ewing sarcoma cell lines (RNA-seq)

Project description:EWSR1-FLI1 is a chimeric transcription factor resulting from the pathognomonic translocation present in Ewing sarcoma cells. Here, we silenced EWSR1-FLI1 in different Ewing sarcoma cell lines. RNA from SKNMC, TC71 and MHH-ES1 cells was extracted 96h post transfection (siCT or siEWSR1-FLI1) or prior doxycycline (day 0) and 7 days after inducing silencing of EWSR1-FLI1 with doxycycline in ASP14 cells. RNA-seq was performed for all conditions.

2022-05-09 | GSE164372 | GEO

EWSR1::FLI1 fusion oncoproteins’ regulation of ETS1 (ChIP-seq)

Project description:Ewing sarcomas harbor few mutations beyond the chromosomal translocation that initiates disease and the mechanistic basis for the metastasis of these tumors remains poorly understood. The epigenome of Ewing sarcoma (EWS) cells reflects the regulatory state of genes associated with the DNA binding activity of the fusion oncoproteins EWSR1::FLI1 or EWSR1::ERG. In this study, we examined the repressive activities of the EWSR1::FLI1/ERG fusion oncoproteins. Focusing on one of the repressed EWSR1::FLI1/ERG target genes, ETS1, we detected EWSR1::FLI1 binding and a H3K27me3 repressive mark at this locus. Depletion of EWSR1::FLI1 results in ETS1’s binding of promoter regions, and we show ETS1 regulates the expression of multiple proteins that function in extracellular matrix organization including TENSIN3 (TNS3). Interestingly, TNS3 expression in EWS tumors significantly correlates with that of ETS1 (0.85, FDR <0.01). TNS3 is a focal adhesion protein that contributes to tumor cell migration by connecting the cytoplasmic tail of integrins to the actin cytoskeleton. EWS cell lines, in which we activated ETS1 expression (CRISPRa) exhibited increased TNS3 expression and a migratory phenotype. Critically, the activated ETS1 EWS cell lines show TNS3 accumulation at leading cell edges, with F-actin cytoskeletal reorganization, a phenotype associated with cell migration.

2024-04-15 | GSE243171 | GEO

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