Synovial sarcoma reprograms transcription by GBAF activation of polycomb targets and loss of CBAF enhancers
Bibliographic record
Abstract
Synovial sarcoma is a cancer driven by a fusion oncoprotein, SS18::SSX, that links SS18, a subunit of BAF-family chromatin remodeling complexes, to the carboxy terminus of SSX, which avidly binds nucleosomes with the histone post-translational modification H2AK119ub. Here, we show in mice that SS18::SSX expression redistributes non-canonical GBAF complexes broadly to promoters and distal enhancers marked by H2AK119ub, which causes developmental loci to lose H3K27me3 and become transcriptionally active. Canonical BAF containing SS18::SSX abandons its typical binding sites, is largely absent from H2AK119ub-marked sites, and instead distributes narrowly to transcription start sites with PBAF. Disruption of Arid1a or Arid1b (both CBAF-specific) retains synovial sarcoma character, while Smarcb1 (PBAF- and CBAF-specific) or Pbrm1 (PBAF-specific) disruption does not, although all accelerate SS18::SSX-driven tumorigenesis in mice. Thus, the synovial sarcomagenesis mechanism involves SS18::SSX reprogramming transcription positively through GBAF redistribution to activate polycomb-targeted developmental genes, and negatively by loss of normal CBAF localization and function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".