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Series GSE108926 Query DataSets for GSE108926
Status Public on Mar 01, 2018
Title The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
 
Overall design Chromatin occupancy by ChIP-Seq of endogenously tagged SS18-SSX (HA-tag), KDM2B, BRG1 and examination of H3K27me3 mark in 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)
 
Contributor(s) Banito A, Lowe SW
Citation(s) 29502955
Submission date Jan 09, 2018
Last update date Mar 27, 2019
Contact name Nicholas D. Socci
Organization name Memorial Sloan Kettering Cancer Center
Department bioinformatics core
Street address 1275 York Ave
City New York
State/province NY
ZIP/Postal code 10065
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (27)
GSM2916088 AB1_HS-SY-II parental line untagged_HA-Tag
GSM2916089 AB10_REN. 713_INPUT for BRG1
GSM2916090 AB11_REN. 713_KDM2B
This SubSeries is part of SuperSeries:
GSE108929 The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma
Relations
BioProject PRJNA429317
SRA SRP128692

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE108926_RAW.tar 6.5 Gb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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