BAF complexes cooperate with lineage-restricted transcription factors to establish cell-state-specific regulatory programs

SMARCB1 reconstitution in atypical teratoid rhabdoid tumor organoids enables lineage-specific TF RFX4 to bind regulatory elements and activate neuronal differentiation programs.

• Why it matters: Although BAF subunit genes are frequently mutated in human cancer, it remains unclear how loss of one subunit yields distinct tumor states.
• What they did: Using integrated multi-omics profiling of patient-derived ATRT organoids and primary tumor tissues, the study combined chromatin accessibility and genome-wide binding with transcriptomics after SMARCB1 reconstitution.
• The result: SMARCB1 restoration directs subtype- and lineage-specific transcriptional and accessibility changes, partially reprogramming ATRT-MYC toward an ATRT-SHH-like identity.

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