Structural basis for BCL7B-mediated ncBAF-nucleosome engagement.

Area of Science:

• Molecular Biology
• Chromatin Biology
• Structural Biology

Background:

• Mammalian SWI/SNF complexes (cBAF, PBAF, ncBAF) remodel nucleosomes using ATP hydrolysis.
• The chromatin interaction mechanisms of cBAF and PBAF are known, but ncBAF remains uncharacterized.
• Understanding ncBAF structure is crucial for elucidating its role in gene regulation.

Purpose of the Study:

• To resolve the molecular architecture of ncBAF-nucleosome complexes.
• To understand the role of BCL7 proteins in ncBAF chromatin engagement.
• To investigate the functional implications of ncBAF's interaction with nuclear actin filaments.

Main Methods:

• Integration of cryo-electron microscopy (cryo-EM).
• Biochemical assays.
• Cross-linking mass spectrometry (XL-MS).

Main Results:

• The conformational transition of ncBAF-nucleosome complexes from nucleotide-free to nucleotide-bound states was resolved.
• BCL7 proteins act as dynamic tethers linking the ARP module to the nucleosomal acidic patch.
• BCL7B enhances ncBAF-mediated remodeling, and β-actin within the ARP module retains ATP hydrolysis activity, potentially linking to nuclear actin networks.

Conclusions:

• BCL7 plays a dynamic role in regulating ncBAF-mediated chromatin remodeling.
• ncBAF exhibits a distinct chromatin engagement mode compared to cBAF/PBAF.
• The findings provide a molecular basis for coordinating nuclear actin with chromatin remodeling.