Regulation of BAF Remodeler Efficiency and the Influence of ARPs,  Super-ejector Mutations, and BRK domain in BAF remodelers

I am working on understanding how the MiniBAF complex and its catalytic ATPase BRG1 regulate DNA translocation, chromatin remodeling, and transcription factor interactions. BRG1 is a central engine of the BAF complex, coupling ATP hydrolysis to DNA movement. My research focuses on how actin-related proteins (ARPs), regulatory domains (BRK), and mutations (STH1 super-ejectors) tune this coupling and remodeling activity. These mechanisms are crucial for proper chromatin architecture, and their disruption contributes to oncogenesis.

Research Objectives

1. Define ARP-driven coupling: Determine how ARPs (and BCL7A) regulate coupling between ATP hydrolysis and DNA translocation in BRG1.
   
   

2. Assess BRK domain function: Investigate how the BRK domain modulates remodeling efficiency and senses proline-rich motifs in transcription factors.
   
   

3. Test “super-ejector” mutations: Evaluate whether STH1 super-ejector mutations are conserved in BRG1 and how they affect DNA translocation, nucleosome sliding/ejection, and nucleosome positioning in vivo.

The methods I am using:

• Biochemical reconstitutions (ATPase and DNA translocation assays)
  
  

• Structural and mutagenesis mapping
  
  

• Sliding/ejection assays (ensemble & single-molecule)
  
  

• Transcription factor peptide/PRM interaction studies
  
  

• Genomic assays: Cut&Tag, ATAC-seq, MNase-seq
  
  

• Cellular phenotyping: EdU, γH2AX, growth