Loss of Snf5 and the formation of an aberrant SWI/SNF complex

Aberrant forms of the SWI/SNF chromatin remodeling complex are associated with human disease. Loss of the Snf5 subunit of SWI/SNF is a driver mutation in pediatric rhabdoid cancers and forms aberrant sub-complexes that are not well characterized. We determined the effects of loss of Snf5 on the composition, nucleosome binding, recruitment and remodeling activities of yeast SWI/SNF. The Snf5 subunit interacts with the ATPase domain of Snf2 and forms a submodule consisting of Snf5, Swp82 and Taf14 as shown by mapping SWI/SNF subunit interactions by crosslinking-mass spectrometry and subunit deletion followed by immunoaffinity chromatography. Snf5 promoted binding of the Snf2 ATPase domain to nucleosomal DNA, enhanced its catalytic activity and facilitated nucleosome remodeling. Snf5 was required for acidic transcription factors to recruit SWI/SNF to chromatin. RNA-seq analysis suggested that both the recruitment and catalytic functions mediated by Snf5 are required for SWI/SNF regulation of gene expression. Overall design: Determining the effects of loss of Snf5 on the composition, nucleosome binding, recruitment, remodeling activities and gene expression profile of yeast SWI/SNF

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Sen P, Luo J, Hada A, Hailu SG, Dechassa ML, Persinger J, Brahma S, Paul S, Ranish J, Bartholomew B