title: Two-color cell array screen reveals interdependent roles for histone chaperones and a chromatin boundary regulator in histone gene repression.
abstract: We describe a fluorescent reporter system that exploits the functional genomic tools available in budding yeast to systematically assess consequences of genetic perturbations on gene expression. We used our Reporter-Synthetic Genetic Array (R-SGA) method to screen for regulators of core histone gene expression. We discovered that the histone chaperone Rtt106 functions in a pathway with two other chaperones, Asf1 and the HIR complex, to create a repressive chromatin structure at core histone promoters. We found that activation of histone (HTA1) gene expression involves both relief of Rtt106-mediated repression by the activity of the histone acetyltransferase Rtt109 and restriction of Rtt106 to the promoter region by the bromodomain-containing protein Yta7. We propose that the maintenance of Asf1/HIR/Rtt106-mediated repressive chromatin domains is the primary mechanism of cell-cycle regulation of histone promoters. Our data suggest that this pathway may represent a chromatin regulatory mechanism that is broadly used across the genome.
authors.affiliation: Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fillingham
authors.forename: Pinay
authors.initials: P
authors.lastname: Kainth
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lambert
authors.forename: Harm
authors.initials: H
authors.lastname: van Bakel
authors.forename: Kyle
authors.initials: K
authors.lastname: Tsui
authors.forename: Lourdes
authors.initials: L
authors.lastname: Peña-Castillo
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
authors.forename: Jack
authors.initials: J
authors.lastname: Greenblatt
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Andrews
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C078808:HIR1 protein, S cerevisiae; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012097:Repressor Proteins; C505157:Rtt106 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C508095:YTA7 protein, S cerevisiae; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae