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

Cell Rep. 2017 Feb 28;18(9):2135-2147. doi: 10.1016/j.celrep.2017.02.017.

Abstract

The SWI/SNF chromatin remodeling complex is highly conserved from yeast to human, and aberrant SWI/SNF complexes contribute to human disease. The Snf5/SMARCB1/INI1 subunit of SWI/SNF is a tumor suppressor frequently lost in pediatric rhabdoid cancers. We examined the effects of Snf5 loss on the composition, nucleosome binding, recruitment, and remodeling activities of yeast SWI/SNF. The Snf5 subunit is shown by crosslinking-mass spectrometry (CX-MS) and subunit deletion analysis to interact with the ATPase domain of Snf2 and to form a submodule consisting of Snf5, Swp82, and Taf14. Snf5 promotes binding of the Snf2 ATPase domain to nucleosomal DNA and enhances the catalytic and nucleosome remodeling activities of SWI/SNF. Snf5 is also required for SWI/SNF recruitment by acidic transcription factors. RNA-seq analysis suggests that both the recruitment and remodeling functions of Snf5 are required in vivo for SWI/SNF regulation of gene expression. Thus, loss of SNF5 alters the structure and function of SWI/SNF.

Keywords: BAF47; Chromatin remodeling; INI1; SMARCB1; SWI/SNF; Snf5.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Cell Nucleus / metabolism
  • Chromatin Assembly and Disassembly / physiology*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / metabolism
  • Gene Expression / physiology
  • Nucleosomes / metabolism
  • Protein Subunits / metabolism
  • Transcription Factors / metabolism*
  • Yeasts / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Fungal Proteins
  • Nucleosomes
  • Protein Subunits
  • Transcription Factors
  • Adenosine Triphosphatases