title: The Ino80 complex prevents invasion of euchromatin into silent chromatin.
abstract: Here we show that the Ino80 chromatin remodeling complex (Ino80C) directly prevents euchromatin from invading transcriptionally silent chromatin within intergenic regions and at the border of euchromatin and heterochromatin. Deletion of Ino80C subunits leads to increased H3K79 methylation and noncoding RNA polymerase II (Pol II) transcription centered at the Ino80C-binding sites. The effect of Ino80C is direct, as it blocks H3K79 methylation by Dot1 in vitro. Heterochromatin stimulates the binding of Ino80C in vitro and in vivo. Our data reveal that Ino80C serves as a general silencing complex that restricts transcription to gene units in euchromatin.
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Yong
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Van
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Suman K
authors.initials: SK
authors.lastname: Pradhan
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Trent
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Jason
authors.initials: J
authors.lastname: Gehrke
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Kuryan
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kitada
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Ajay
authors.initials: A
authors.lastname: Vashisht
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Nancy
authors.initials: N
authors.lastname: Tran
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: James
authors.initials: J
authors.lastname: Wohlschlegel
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Peterson
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA;
authors.forename: Siavash K
authors.initials: SK
authors.lastname: Kurdistani
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095, USA; mcarey@mednet.ucla.edu.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Carey
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000235:genetics*; D022041:Euchromatin / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D008745:Methylation; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D002843:Chromatin; D022041:Euchromatin; C483404:INO80 complex, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; D012319:RNA Polymerase II
keywords: Dot1; H3K79 methylation; Ino80; Sir proteins; heterochromatin; silencing