title: SWI/SNF-like chromatin remodeling factor Fun30 supports point centromere function in S. cerevisiae.
abstract: Budding yeast centromeres are sequence-defined point centromeres and are, unlike in many other organisms, not embedded in heterochromatin. Here we show that Fun30, a poorly understood SWI/SNF-like chromatin remodeling factor conserved in humans, promotes point centromere function through the formation of correct chromatin architecture at centromeres. Our determination of the genome-wide binding and nucleosome positioning properties of Fun30 shows that this enzyme is consistently enriched over centromeres and that a majority of CENs show Fun30-dependent changes in flanking nucleosome position and/or CEN core micrococcal nuclease accessibility. Fun30 deletion leads to defects in histone variant Htz1 occupancy genome-wide, including at and around most centromeres. FUN30 genetically interacts with CSE4, coding for the centromere-specific variant of histone H3, and counteracts the detrimental effect of transcription through centromeres on chromosome segregation and suppresses transcriptional noise over centromere CEN3. Previous work has shown a requirement for fission yeast and mammalian homologs of Fun30 in heterochromatin assembly. As centromeres in budding yeast are not embedded in heterochromatin, our findings indicate a direct role of Fun30 in centromere chromatin by promoting correct chromatin architecture.
authors.affiliation: Nuclear Dynamics, Babraham Institute, Cambridge, United Kingdom.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Durand-Dubief
authors.forename: William Ryan
authors.initials: WR
authors.lastname: Will
authors.forename: Edoardo
authors.initials: E
authors.lastname: Petrini
authors.forename: Delphine
authors.initials: D
authors.lastname: Theodorou
authors.forename: Rachael R
authors.initials: RR
authors.lastname: Harris
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Crawford
authors.forename: Konrad
authors.initials: K
authors.lastname: Paszkiewicz
authors.forename: Felix
authors.initials: F
authors.lastname: Krueger
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Correra
authors.forename: Anna T
authors.initials: AT
authors.lastname: Vetter
authors.forename: J Ross
authors.initials: JR
authors.lastname: Miller
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kent
authors.forename: Patrick
authors.initials: P
authors.lastname: Varga-Weisz
mesh_terms: D002503:Centromere / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D018386:Kinetochores; D009707:Nucleosomes / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C092746:CSE4 protein, S cerevisiae; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C074000:FUN30 protein, S cerevisiae; D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors