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

UID: 10497

Description
From GEO Summary and overall design: 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.
ATAC-Seq of human synovial sarcoma cells (HS-SY-II) in control cells (Ren.173) and upon knockdown of SS18-SSX1 (SSX.1274) or of KDM2B (KDM2B. 4395)
Subject of Study
Subject(s)
OncoTree Cancer Type(s)
Synovial Sarcoma
Access via GEO

Subseries of GEO SuperSeries GSE108929
Accession #: GSE108927

Access via SRA

ATAC Sequence reads for 3 samples.
Accession #: SRP128694

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA429316

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus database provides open access to these files.
Associated Publications
Data Type
Equipment Used
Illumina HiSeq 2000
Dataset Format(s)
SRA, TAR, BIGWIG
Dataset Size
1.6 GB (TAR of BIGWIG), 4.7 GB (SRA)
Data Catalog Record Updated
2021-11-04