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

Area of Science:

• Molecular Biology
• Chromatin Biology
• Gene Regulation

Background:

• BAF (SWI/SNF) complexes are critical chromatin remodelers that regulate DNA accessibility through interactions with various binding partners.
• The precise mechanisms underlying BAF's interactions with diverse partners, particularly scaffold proteins, remain incompletely understood.

Purpose of the Study:

• To investigate the role of scaffold proteins, specifically beta-catenin (CTNNB1), in mediating interactions between BAF complexes and transcription factors.
• To elucidate the molecular basis for how beta-catenin bridges BAF and transcription factors like steroidogenic factor 1 (SF-1, NR5A1).

Main Methods:

• Investigated the effects of BAF inhibition on SF-1/beta-catenin enhancer occupancy and target gene activation.
• Utilized molecular visualization techniques to examine protein-protein interactions.
• Assessed beta-catenin's role as an adapter linking BAF to multiple transcription factors including YAP1, SOX2, FOXO3, and CBP/p300.

Main Results:

• BAF inhibition disrupted SF-1/beta-catenin enhancer occupancy and impaired SF-1 target gene activation.
• Beta-catenin functions as a molecular adapter, connecting SF-1 to the intrinsically disordered region (IDR) of the BAF subunit ARID1A via its Armadillo repeats.
• Beta-catenin was identified as a general adapter linking BAF to other factors, including YAP1, SOX2, FOXO3, and CBP/p300, through an IDR-mediated mechanism.

Conclusions:

• Beta-catenin serves as a critical molecular adapter, facilitating the modular coordination of BAF chromatin remodelers with diverse transcription factors.
• This adapter mechanism, involving beta-catenin and ARID1A's IDR, is essential for regulating gene accessibility and transcriptional outcomes.
• The findings reveal a general principle of how intrinsically disordered regions and adapter proteins enable dynamic interactions within the BAF interactome.