title: Expression homeostasis during DNA replication.
abstract: Genome replication introduces a stepwise increase in the DNA template available for transcription. Genes replicated early in S phase experience this increase before late-replicating genes, raising the question of how expression levels are affected by DNA replication. We show that in budding yeast, messenger RNA (mRNA) synthesis rate is buffered against changes in gene dosage during S phase. This expression homeostasis depends on acetylation of H3 on its internal K56 site by Rtt109/Asf1. Deleting these factors, mutating H3K56 or up-regulating its deacetylation, increases gene expression in S phase in proportion to gene replication timing. Therefore, H3K56 acetylation on newly deposited histones reduces transcription efficiency from replicated DNA, complementing its role in guarding genome stability. Our study provides molecular insight into the mechanism maintaining expression homeostasis during DNA replication.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Voichek
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Bar-Ziv
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. naama.barkai@weizmann.ac.il.
authors.forename: Naama
authors.initials: N
authors.lastname: Barkai
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics / Q000502:physiology*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D018628:Gene Dosage; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D042822:Genomic Instability; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics*; D018832:Molecular Chaperones / Q000378:metabolism; D012331:RNA, Fungal / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013698:Templates, Genetic
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D006657:Histones; D018832:Molecular Chaperones; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae; D012321:DNA-Directed RNA Polymerases