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

• Published in: Cell reports (Cambridge) 2017-02, Vol.18 (9), p.2135-2147
• Main Authors: Sen, Payel, Luo, Jie, Hada, Arjan, Hailu, Solomon G., Dechassa, Mekonnen Lemma, Persinger, Jim, Brahma, Sandipan, Paul, Somnath, Ranish, Jeff, Bartholomew, Blaine
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - metabolism; BAF47; Cell Nucleus - metabolism; Chromatin Assembly and Disassembly - physiology; Chromatin remodeling; Chromosomal Proteins, Non-Histone - metabolism; DNA-Binding Proteins - metabolism; Fungal Proteins - metabolism; Gene Expression - physiology; INI1; Nucleosomes - metabolism; Protein Subunits - metabolism; SMARCB1; Snf5; SWI/SNF; Transcription Factors - metabolism; Yeasts - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.02.017

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. [Display omitted] •Transcription defects because of the loss of Snf5 are not the same as the loss of SWI/SNF•Snf5 has a scaffolding role and is required for Taf14 and Swp82 to be in SWI/SNF•Snf5 interacts with the ATPase domain of Snf2 and promotes its binding to DNA•Snf5 is essential for SWI/SNF recruitment by the Gal4-VP16 transcription factor Mutation of SWI/SNF chromatin remodeling complex subunits contributes to cancer and neurological disorders. Sen et al. report that loss of the Snf5 subunit alters the architecture and function of SWI/SNF in a yeast model system. These findings may reflect changes that occur in pediatric rhabdoid tumors with mutated Snf5.