BAF (SWI/SNF) chromatin remodelers engage binding partners to generate site-specific DNA accessibility. However, the basis for interaction 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 (CTNNB1) and steroidogenic factor 1 (SF-1, NR5A1), a transcription factor central to steroid production in human cells. BAF inhibition rapidly opposed SF-1/β-catenin enhancer occupancy, impairing SF-1 target activation and SF-1/β-catenin autoregulation. These effects arise due to β-catenin's role as a molecular adapter between SF-1 and an intrinsically disordered region (IDR) of the canonical BAF (cBAF) subunit ARID1A. In contrast to exclusively IDR-driven mechanisms, adapter function is mediated by direct association of ARID1A with β-catenin's folded Armadillo repeats. β-catenin similarly linked cBAF to YAP1, SOX2, FOXO3, and CBP/p300, reflecting a general IDR-mediated mechanism for modular coordination between factors. Molecular visualization highlights β-catenin's adapter role for interaction of cBAF with binding partners.

Advanced Technology Cores Baylor College of Medicine Houston TX 77030 USA

Center for Precision Environmental Health Baylor College of Medicine Houston TX 77030 USA; Department of Biochemistry and Molecular Pharmacology Baylor College of Medicine Houston TX 77030 USA

Department of Endocrine Neoplasia and Hormonal Disorders The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Department of Internal Medicine Division of Metabolism Endocrinology and Diabetes University of Michigan Ann Arbor MI 48105 USA

Department of Internal Medicine Division of Metabolism Endocrinology and Diabetes University of Michigan Ann Arbor MI 48105 USA; Endocrine Oncology Program Rogel Cancer Center University of Michigan Health System Ann Arbor MI 48109 USA

Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA; Advanced Technology Cores Baylor College of Medicine Houston TX 77030 USA; Dan L Duncan Comprehensive Cancer Center Baylor College of Medicine Houston TX 77030 USA

Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA; Center for Precision Environmental Health Baylor College of Medicine Houston TX 77030 USA

Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA; Center for Precision Environmental Health Baylor College of Medicine Houston TX 77030 USA; Dan L Duncan Comprehensive Cancer Center Baylor College of Medicine Houston TX 77030 USA; Department of Bioengineering Rice University Houston TX 77030 USA

Department of Pathology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Division of Endocrinology Metabolism and Diabetes Department of Medicine University of Colorado School of Medicine at Colorado Anschutz Medical Campus Aurora CO 80045 USA; Research Service Rocky Mountain Regional Veterans Affairs Medical Center Aurora CO 80045 USA

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic; Department of Cell Biology Faculty of Science Charles University Prague Czech Republic

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