title: Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters.
abstract: Precise nucleosome-positioning patterns at promoters are thought to be crucial for faithful transcriptional regulation. However, the mechanisms by which these patterns are established, are dynamically maintained, and subsequently contribute to transcriptional control are poorly understood. The switch/sucrose non-fermentable chromatin remodeling complex, also known as the Brg1 associated factors complex, is a master developmental regulator and tumor suppressor capable of mobilizing nucleosomes in biochemical assays. However, its role in establishing the nucleosome landscape in vivo is unclear. Here we have inactivated Snf5 and Brg1, core subunits of the mammalian Swi/Snf complex, to evaluate their effects on chromatin structure and transcription levels genomewide. We find that inactivation of either subunit leads to disruptions of specific nucleosome patterning combined with a loss of overall nucleosome occupancy at a large number of promoters, regardless of their association with CpG islands. These rearrangements are accompanied by gene expression changes that promote cell proliferation. Collectively, these findings define a direct relationship between chromatin-remodeling complexes, chromatin structure, and transcriptional regulation.
authors.affiliation: Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tolstorukov
authors.forename: Courtney G
authors.initials: CG
authors.lastname: Sansam
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Edward C
authors.initials: EC
authors.lastname: Koellhoffer
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Helming
authors.forename: Burak H
authors.initials: BH
authors.lastname: Alver
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Tillman
authors.forename: Julia A
authors.initials: JA
authors.lastname: Evans
authors.forename: Boris G
authors.initials: BG
authors.lastname: Wilson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.forename: Charles W M
authors.initials: CW
authors.lastname: Roberts
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002843:Chromatin / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D018899:CpG Islands / Q000502:physiology; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D009707:Nucleosomes; D000071796:SMARCB1 Protein; C513265:Smarcb1 protein, mouse; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases