title: Cell cycle-regulated oscillator coordinates core histone gene transcription through histone acetylation.
abstract: DNA replication occurs during the synthetic (S) phase of the eukaryotic cell cycle and features a dramatic induction of histone gene expression for concomitant chromatin assembly. Ectopic production of core histones outside of S phase is toxic, underscoring the critical importance of regulatory pathways that ensure proper expression of histone genes. Several regulators of histone gene expression in the budding yeast Saccharomyces cerevisiae are known, yet the key oscillator responsible for restricting gene expression to S phase has remained elusive. Here, we show that suppressor of Ty (Spt)10, a putative histone acetyltransferase, and its binding partner Spt21 are key determinants of S-phase-specific histone gene expression. We show that Spt21 abundance is restricted to S phase in part by anaphase promoting complex Cdc20-homologue 1 (APC(Cdh1)) and that it is recruited to histone gene promoters in S phase by Spt10. There, Spt21-Spt10 enables the recruitment of a cascade of regulators, including histone chaperones and the histone-acetyltransferase general control nonderepressible (Gcn) 5, which we hypothesize lead to histone acetylation and consequent transcription activation.
authors.affiliation: The Donnelly Center, University of Toronto, Toronto, ON, Canada M5S 3E1;
authors.forename: Christoph F
authors.initials: CF
authors.lastname: Kurat
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lambert
authors.affiliation: The Donnelly Center, University of Toronto, Toronto, ON, Canada M5S 3E1;
authors.forename: Julia
authors.initials: J
authors.lastname: Petschnigg
authors.affiliation: The Donnelly Center, University of Toronto, Toronto, ON, Canada M5S 3E1;
authors.forename: Helena
authors.initials: H
authors.lastname: Friesen
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 3E1; and.
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.affiliation: The Donnelly Center, University of Toronto, Toronto, ON, Canada M5S 3E1;
authors.forename: Adam
authors.initials: A
authors.lastname: Rosebrock
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 3E1; and.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
authors.affiliation: Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada M5B 2K3.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fillingham
authors.affiliation: The Donnelly Center, University of Toronto, Toronto, ON, Canada M5S 3E1; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 3E1; and brenda.andrews@utoronto.ca.
authors.forename: Brenda
authors.initials: B
authors.lastname: Andrews
mesh_terms: D000107:Acetylation; D002453:Cell Cycle; D004261:DNA Replication / Q000235:genetics; D004271:DNA, Fungal / Q000096:biosynthesis / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D016196:S Phase / Q000235:genetics* / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004271:DNA, Fungal; D006657:Histones; C086445:SPT21 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C086444:SPT10 protein, S cerevisiae