β-catenin functions as a molecular adapter for disordered cBAF interactions

BAF (SWI/SNF) chromatin remodelers engage binding partners to generate sitespecific DNA accessibility. However, the basis for interactions between BAF and divergent binding partners has remained unclear. Here we tested the hypothesis that scaffold proteins augment BAF’s binding repertoire by examining β-catenin and steroidogenic factor-1 (SF-1, NR5A1), a β-catenin–dependent transcription factor central to steroid production. In steroidogenic cell lines, BAF inhibition rapidly opposed overlapping SF-1/β-catenin enhancer occupancy, thereby impairing SF-1 target activation, steroid production, and SF-1/β-catenin autoregulation. These effects arise due to β-catenin’s role as an adapter between SF-1 and an intrinsically disordered region (IDR) of the canonical BAF (cBAF) subunit ARID1A. In contrast to exclusively IDR-driven mechanisms, folded Armadillo repeats on β-catenin were required to bind cBAF. β-catenin similarly linked cBAF to SOX2, FOXO3, YAP1, and CBP/p300. Visualization of contacts highlighted β-catenin’s central role in IDR-dependent interaction of cBAF with diverse transcription factors and chromatin regulators. The cross-linking dataset was used to validate the interaction interface obtained with computational modelling.