Composition and Function of Mutant Swi/Snf Complexes

Abstract

Summary: The 12-subunit Swi/Snf chromatin remodeling complex is conserved from yeast to humans. It functions to alter nucleosome positions by either sliding nucleosomes on DNA or evicting histones. Interestingly, 20% of all human cancers carry mutations in subunits of the Swi/Snf complex. Many of these mutations cause protein instability and loss, resulting in partial Swi/Snf complexes. Although several studies have shown that histone acetylation and activator-dependent recruitment of Swi/Snf regulate its function, it is less well understood how subunits regulate stability and function of the complex. Using functional proteomic and genomic approaches, we have assembled the network architecture of yeast Swi/Snf. In addition, we find that subunits of the Swi/Snf complex regulate occupancy of the catalytic subunit Snf2, thereby modulating gene transcription. Our findings have direct bearing on how cancer-causing mutations in orthologous subunits of human Swi/Snf may lead to aberrant regulation of gene expression by this complex. : Subunits of the Swi/Snf chromatin-remodeling complex are mutated in 20% of cancers. Dutta et al. report modularity within yeast Swi/Snf that regulates both architecture and genomic functions of the complex. These findings will help predict complex composition in diseased states where subunits of the complex are mutated. Keywords: modularity, architecture, Swi/Snf complex, patterns, gene expression, targeting, Snf2 occupancy, Swi/Snf subunits, residual Swi/Snf complexes, cancer