GEO series

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [BR_ChIP-seq]

GSE266060 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 11 samples Submitted 2025/08/06 Platform GPL24676

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 11 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Homo sapiens (human)
Samples: 11 samples
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Targeting SUMOylation promotes cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcomaNature communications · 2025

Summary (written by the submitters)

Synovial Sarcoma (SS) is driven by the SS18::SSX translocation event and is often diagnosed in patients under 30. In general, SS is refractory to chemotherapy and other therapeutic approaches. SS18::SSX does not directly bind to DNA. Instead, SS18::SSX alters ATP-dependent chromatin remodeling complex BAF (mammalian SWI/SNF complex) complexes away from a wild-type SS18-containing canonical (cBAF) complex towards a SS18::SSX-containing non-canonical (nc)BAF complex to drive a SS-specific transcription program with subsequent tumor formation.

Read the full summary ↓

Small molecule targeted therapies are expanding beyond the kinome, providing additional tools to treat cancers that are not yet amenable to targeted therapies. Here, we demonstrate that SS18::SSX activates the SUMOylation program and SS are sensitive to the small molecule SAE1/2 inhibitor, TAK-981 (subasumstat). Mechanistically, we demonstrate TAK-981 de-SUMOylates the cBAF and Polybromo-associated BAF complex (PBAF) complex member, SMARCE1. The result of which is stabilization and restoration of cBAF complexes on chromatin, shifting away from the dominant SS18::SSX-ncBAF-complex driven transcriptome. This phenotypic shift is associated with DNA damage and cell death, resulting in tumor inhibition across both human and mouse SS tumor models. As such, TAK-981 combined with standard-of-care chemotherapy enhances induced synergistic activity through increased DNA damage, leading to tumor regressions. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX-ncBAF transcriptome, identifying a therapeutic vulnerability in SS, and positioning the in-clinic TAK-981 as a novel candidate to treat this refractory cancer.

Published in

Targeting SUMOylation promotes cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma

Floros KV, Fairchild CK Jr, Li J et al. · Nature communications 2025 · PMID 41193430 · doi:10.1038/s41467-025-64665-8

This dataset

Open GSE266060 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE266060_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1105621 and SRA study SRP504477. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41193430) ↗

Samples in this study

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+ 11 more — browse all 11 samples with per-sample file links →

Datasets on a similar topic

GSE266199 Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [HSH3_ChIP-seq_HS-SY-II] 9 samples shares ss18, ssx, stabilization, sumoylation, disruption, targeting, synovial, chip-seq
GSE266064 Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [HSJHD_ChIP-seq] 7 samples shares ss18, ssx, stabilization, sumoylation, disruption, targeting, synovial, chip-seq
GSE266063 Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [HS18_ChIP-seq] 7 samples shares ss18, ssx, stabilization, sumoylation, disruption, targeting, synovial, chip-seq
GSE266201 Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [HSH3_ChIP-seq_SYO-1] 7 samples shares ss18, ssx, stabilization, sumoylation, disruption, targeting, synovial, chip-seq
GSE266134 Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [SYATAC_ATAC-seq] 6 samples shares ss18, ssx, stabilization, sumoylation, disruption, targeting, synovial
GSE266203 Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [RNA-seq_HS-SY-II] 8 samples shares ss18, ssx, stabilization, sumoylation, disruption, targeting, synovial
GSE266207 Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [SSPDX.RNA-seq] 6 samples shares ss18, ssx, stabilization, sumoylation, disruption, targeting, synovial
GSE328411 ChIP-seq of GLTSCR1 and SS18::SSX fusion in HS-SY-II synovial sarcoma cells treated with the BRD9 PROTAC degrader WA-68 across a time course 14 samples shares ss18, ssx, synovial, chip-seq

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