β-Catenin Functions as a Molecular Adapter for Disordered cBAF Interactions

Authors

• Yuen San Chan
• Qinyu Gao
• Sarah A Robinson
• Wenzhi Wang
• Ruzena Filandrova
• Lisa-Maria Weinhold
• Mario Loeza Cabrera
• Miao Zhang
• Chandra Shekar R Ambati
• Antonio M Lerario
• Nagireddy Putluri
• Katja Kiseljak-Vassiliades
• Margaret E Wierman
• Mouhammed Amir Habra
• Gary D Hammer
• Vaclav Veverka
• Katerina Cermakova
• H Courtney Hodges

Language

English

Publication Date

8-21-2025

Journal

Molecular Cell

DOI

10.1016/j.molcel.2025.06.026

PMID

40695292

PMCID

PMC12323811

PubMedCentral® Posted Date

7-21-2026

PubMedCentral® Full Text Version

Author MSS

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

Humans, beta Catenin, Transcription Factors, Steroidogenic Factor 1, DNA-Binding Proteins, Protein Binding, HEK293 Cells, Adaptor Proteins, Signal Transducing, YAP-Signaling Proteins, Forkhead Box Protein O3, Intrinsically Disordered Proteins, p300-CBP Transcription Factors, Nuclear Proteins, Phosphoproteins, Binding Sites, Enhancer Elements, Genetic, Signal Transduction

Published Open-Access

yes

Recommended Citation

Chan, Yuen San; Gao, Qinyu; Robinson, Sarah A; et al., "β-Catenin Functions as a Molecular Adapter for Disordered cBAF Interactions" (2025). Faculty, Staff and Students Publications. 3097.
https://digitalcommons.library.tmc.edu/baylor_docs/3097