title: The SWI/SNF tumor suppressor complex: Regulation of promoter nucleosomes and beyond.
abstract: Nucleosomes, octamers of histones wrapped in 147 bp of DNA, are the basic unit of chromatin. In eukaryotic cells, the placement of nucleosomes along the genome is highly organized, and modulation of this ordered arrangement contributes to regulation of gene expression. The SWI/SNF complex utilizes the energy of ATP hydrolysis to mobilize nucleosomes and remodel chromatin structure. Recently, the complex has also been implicated in oncogenesis as genes encoding multiple SWI/SNF subunits have been found mutated at high frequency across a wide spectrum of cancers. Given that epigenetic aberrations are now characterized as a hallmark of human cancer, hypotheses have been put forth that the SWI/SNF complex inhibits tumor formation by regulating key chromatin functions. To understand how the SWI/SNF complex contributes to nucleosome organization in vivo we performed a genome-wide study in mammalian cells. We found that inactivation of SWI/SNF subunits leads to disruptions of specific nucleosome patterning and a loss of nucleosome occupancy at a large number of promoters. These findings define a direct relationship between the SWI/SNF complex, chromatin structure, and transcriptional regulation. In this extra view, we discuss our findings, their relevance to gene regulation, and possible links to the tumor suppression activities of the SWI/SNF complex.
authors.affiliation: Department of Pediatric Oncology; Dana-Farber Cancer Institute; Boston, MA USA; Division of Hematology/Oncology; Boston Children's Hospital; Boston, MA USA; Department of Pediatrics; Harvard Medical School; Boston, MA USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Charles W M
authors.initials: CW
authors.lastname: Roberts
mesh_terms: D000818:Animals; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009707:Nucleosomes; D025521:Tumor Suppressor Proteins
keywords: BAF47; Brg1; SMARCA4; SMARCB1; SNF5; SWI/SNF; chromatin remodeling; epigenetic instability; nucleosome