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Identification of assembly mode of non-canonical BAF (ncBAF) chromatin remodeling complex core module

Qinling Mo1, Beibei Liu1, Chunyu Liu1

  • 1State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, and College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China.

Biochemical and Biophysical Research Communications
|December 28, 2024
PubMed

Insights

Researchers elucidated the assembly of the non-canonical BAF (ncBAF) complex, a crucial chromatin remodeler implicated in cancer. They identified key protein interactions and assembled the ncBAF core module, paving the way for structural studies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Mammalian SWI/SNF (mSWI/SNF) complexes are ATP-dependent chromatin remodelers vital for gene regulation.
  • Mutations in mSWI/SNF genes are found in over 20% of human cancers.
  • The non-canonical BAF (ncBAF) complex's organization and assembly are poorly understood compared to other mSWI/SNF classes.

Purpose of the Study:

  • To investigate the modular organization and assembly mechanism of the ncBAF complex.
  • To identify interacting protein fragments within the ncBAF complex.
  • To assemble the core ncBAF module in vitro.

Main Methods:

  • Fragment mapping of SMARCC1/SMARCD1 complex interactions.
  • Purification of tetrameric and quinary ncBAF complexes using recombinant proteins.
  • In vitro assembly of the ncBAF core module.

Main Results:

  • Identified a stable complex formed by GLTSCR1(1041-1204) with SMARCC1(447-966)/SMARCD1(129-515).
  • Purified a tetrameric complex containing SMARCC1, SMARCD1, GLTSCR1, and BRD9.
  • Successfully assembled a stable quinary complex, representing the ncBAF core module, in vitro.

Conclusions:

  • Provided insights into the assembly process of the ncBAF complex.
  • Established the foundation for future structural determination of the ncBAF complex.
  • Highlighted the importance of understanding ncBAF complex assembly in the context of cancer biology.
Keywords:
Chromatin remodeling complexCore moduleSMARCC1/SAMRCD1/BRD9/GLTSCR1/SMARCA4 complexSWI/SNF complexncBAF

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