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. 2025 Aug 21;85(16):3041-3056.e9.
doi: 10.1016/j.molcel.2025.06.026. Epub 2025 Jul 21.

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

Yuen San Chan  1 , Qinyu Gao  1 , Sarah A Robinson  1 , Wenzhi Wang  1 , Ruzena Filandrova  2 , Lisa-Maria Weinhold  3 , Mario Loeza Cabrera  1 , Miao Zhang  4 , Chandra Shekar R Ambati  5 , Antonio M Lerario  6 , Nagireddy Putluri  7 , Katja Kiseljak-Vassiliades  8 , Margaret E Wierman  8 , Mouhammed Amir Habra  9 , Gary D Hammer  10 , Vaclav Veverka  3 , Katerina Cermakova  11 , H Courtney Hodges  12
Affiliations

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

Yuen San Chan et al. Mol Cell. .

Abstract

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.

Keywords: IDRs; adrenocortical carcinoma; chromatin remodeling; co-activators; scaffold proteins; steroid hormones; transcription factors; transcription regulators; unstructured protein.

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Conflict of interest statement

Declaration of interests G.D.H. reports unrelated personal fees from Radionetics and Orphagen Pharmaceuticals for consultation on projects outside the scope of this work.

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