The SOX9 C-terminus encodes a transferable cBAF-recruitment module for enhancer remodeling and cell-state control

SOX9’s intrinsically disordered C-terminus recruits SMARCB1-containing cBAF to stem-like enhancers during APC-mutant adenoma formation, and its loss displaces cBAF from ~80% of co-bound enhancers.

• Why it matters: It remains unclear how transcription factor DNA occupancy is translated into cell-state-specific chromatin accessibility by recruiting the right remodelers.
• What they did: The study used acute, reversible SOX9 degradation and C-terminal truncations in APC-mutant adenoma models, then tested rescue by SOX9 re-expression, SMARCB1 docking, and COMET fusion to dCas9.
• The result: SOX9 degradation collapses enhancer accessibility and stem-like identity, while restoring SOX9 or enforcing SMARCB1 docking partially rescues cBAF recruitment, accessibility, stem-like transcription, and organoid self-renewal.

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