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The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE108929 | GEO | 2018/03/01

REPOSITORIES: GEO

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The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma.

Project description:Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands. Via KDM2B, SS18-SSX1 binds and aberrantly activates expression of developmentally regulated genes otherwise targets of polycomb-mediated repression, which is restored upon KDM2B depletion, leading to irreversible mesenchymal differentiation. Thus, SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression.

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The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [RNA-seq]

Project description:Gene fusions arising from chromosomal translocations are key oncogenic drivers in soft tissue sarcomas but little is known about how they exert their oncogenic effects. Our study explores the molecular mechanisms by which the SS18-SSX fusion oncoprotein subverts epigenetic mechanisms of gene regulation to drive synovial sarcoma. Using functional genomics, we identify KDM2B – a histone demethylase and core component of a non-canonical Polycomb Repressive Complex 1 (PRC1.1) – as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands genome-wide. Via KDM2B, SS18-SSX binds and aberrantly activates expression of a series of developmentally regulated transcription factors that would otherwise be targets of polycomb-mediated repression, which is restored upon KDM2B depletion leading to irreversible mesenchymal differentiation. Thus, SS18-SSX de-regulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression.

2018-03-01 | GSE108928 | GEO

The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [ATAC-seq]

2018-03-01 | GSE108927 | GEO

The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [ChIP-seq]

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The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma.

Project description:Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.

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The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma

Project description:The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma

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The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [RNA-seq]

Project description:The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [RNA-seq]

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The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [ATAC-seq]

Project description:The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [ATAC-seq]

| PRJNA429316 | ENA

The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [ChIP-seq]

Project description:The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [ChIP-seq]