title: Restriction of histone gene transcription to S phase by phosphorylation of a chromatin boundary protein.
abstract: The cell cycle-regulated expression of core histone genes is required for DNA replication and proper cell cycle progression in eukaryotic cells. Although some factors involved in histone gene transcription are known, the molecular mechanisms that ensure proper induction of histone gene expression during S phase remain enigmatic. Here we demonstrate that S-phase transcription of the model histone gene HTA1 in yeast is regulated by a novel attach-release mechanism involving phosphorylation of the conserved chromatin boundary protein Yta7 by both cyclin-dependent kinase 1 (Cdk1) and casein kinase 2 (CK2). Outside S phase, integrity of the AAA-ATPase domain is required for Yta7 boundary function, as defined by correct positioning of the histone chaperone Rtt106 and the chromatin remodeling complex RSC. Conversely, in S phase, Yta7 is hyperphosphorylated, causing its release from HTA1 chromatin and productive transcription. Most importantly, abrogation of Yta7 phosphorylation results in constitutive attachment of Yta7 to HTA1 chromatin, preventing efficient transcription post-recruitment of RNA polymerase II (RNAPII). Our study identified the chromatin boundary protein Yta7 as a key regulator that links S-phase kinases with RNAPII function at cell cycle-regulated histone gene promoters.
authors.affiliation: The Donnelly Center, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Christoph F
authors.initials: CF
authors.lastname: Kurat
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lambert
authors.forename: Dewald
authors.initials: D
authors.lastname: van Dyk
authors.forename: Kyle
authors.initials: K
authors.lastname: Tsui
authors.forename: Harm
authors.initials: H
authors.lastname: van Bakel
authors.forename: Supipi
authors.initials: S
authors.lastname: Kaluarachchi
authors.forename: Helena
authors.initials: H
authors.lastname: Friesen
authors.forename: Pinay
authors.initials: P
authors.lastname: Kainth
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fillingham
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Andrews
mesh_terms: D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D016196:S Phase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; C508095:YTA7 protein, S cerevisiae; D047390:Casein Kinase II; D016203:CDC2 Protein Kinase