title: Composition and Function of Mutant Swi/Snf Complexes.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, 120 Flagg Road, Kingston, RI 02881, USA. Electronic address: arnob@uri.edu.
authors.forename: Arnob
authors.initials: A
authors.lastname: Dutta
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Sardiu
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Gogol
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Gilmore
authors.affiliation: Institute of Cancer Biological Therapy, Xuzhou Medical University, Jiangsu 221002, China.
authors.forename: Daoyong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abmayr
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. Electronic address: jlw@stowers.org.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D002384:Catalysis; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D023281:Genomics / Q000379:methods; D006657:Histones / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics; D040901:Proteomics / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009707:Nucleosomes; D021122:Protein Subunits; C445179:SWI-SNF-B chromatin-remodeling complex; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C499333:SNF2 protein, S cerevisiae
keywords: Snf2 occupancy; Swi/Snf complex; Swi/Snf subunits; architecture; cancer; gene expression; modularity; patterns; residual Swi/Snf complexes; targeting