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Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex

Payel Sen1, Jie Luo2, Arjan Hada3

  • 1Department of Biochemistry and Molecular Biology, Southern Illinois University, Carbondale, IL 62901, USA.

Cell Reports
|March 2, 2017
PubMed

Insights

Loss of the Snf5 subunit in yeast SWI/SNF chromatin remodeling complexes alters complex structure and function. Snf5 is crucial for DNA binding, gene regulation, and overall SWI/SNF activity.

Area of Science:

  • Molecular Biology
  • Chromatin Biology
  • Epigenetics

Background:

  • The SWI/SNF chromatin remodeling complex is essential for gene regulation and is conserved across eukaryotes.
  • Aberrant SWI/SNF function is linked to human diseases, including pediatric cancers.
  • The Snf5 subunit (SMARCB1/INI1) is a key component and its loss is associated with tumor suppression.

Purpose of the Study:

  • To investigate the functional role of the Snf5 subunit in yeast SWI/SNF complex.
  • To elucidate how Snf5 loss impacts SWI/SNF composition, DNA binding, and remodeling activity.
  • To understand Snf5's contribution to SWI/SNF recruitment and gene expression regulation.

Main Methods:

  • Crosslinking-mass spectrometry (CX-MS) to identify protein interactions.
  • Subunit deletion analysis to assess the impact of Snf5 removal.
  • Nucleosome binding and remodeling assays.
  • RNA-sequencing (RNA-seq) for gene expression analysis.

Main Results:

  • Snf5 interacts with the Snf2 ATPase domain and forms a stable submodule with Swp82 and Taf14.
  • Snf5 enhances Snf2's binding to nucleosomal DNA and boosts catalytic and remodeling activities.
  • Snf5 is essential for SWI/SNF recruitment by acidic transcription factors and in vivo gene regulation.

Conclusions:

  • Snf5 is a critical regulator of yeast SWI/SNF structure and function.
  • Snf5's roles in DNA binding, recruitment, and remodeling are vital for SWI/SNF-mediated gene expression.
  • Understanding Snf5's function provides insights into SWI/SNF-related human diseases.

Keywords:
BAF47Chromatin remodelingINI1SMARCB1SWI/SNFSnf5

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