title: A new role for the transcriptional corepressor SIN3; regulation of centromeres.
abstract: Centromeres play a vital role in maintaining the genomic stability of eukaryotes by coordinating the equal distribution of chromosomes to daughter cells during mitosis and meiosis. Fission yeast (S. pombe) centromeres consist of a 4-9 kb central core region and 30-100 kb of flanking inner (imr/B) and outer (otr/K) repeats. These sequences direct a laminar kinetochore structure similar to that of human centromeres. Centromeric heterochromatin is generally underacetylated. We have previously shown that inhibition of histone deacetylases (HDACs) caused hyperacetylation of centromeres and defective chromosome segregation. SIN3 is a HDAC corepressor that has the ability to mediate HDAC targeting in the repression of promoters. In this study, we have characterized S. pombe sin three corepressors (Pst1p and Pst2p) to investigate whether SIN3-HDAC is required in the regulation of centromeres. We show that only pst1-1 and not pst2Delta cells displayed anaphase defects and thiabendazole sensitivity. pst1-1 cells showed reduced centromeric silencing, increased histone acetylation in centromeric chromatin, and defective centromeric sister chromatid cohesion. The HDAC Clr6p and Pst1p coimmunoprecipitated, and Pst1p colocalized with centromeres, particularly in binucleate cells. These data are consistent with a model in which Pst1p-Clr6p temporally associate with centromeres to carry out the initial deacetylation necessary for subsequent steps in heterochromatin formation.
authors.affiliation: Karolinska Institutet, Department of Biosciences Novum, University College Sodertorn, Department of Natural Sciences, S-141 89, Huddinge, Sweden.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Silverstein
authors.forename: William
authors.initials: W
authors.lastname: Richardson
authors.forename: Henry
authors.initials: H
authors.lastname: Levin
authors.forename: Robin
authors.initials: R
authors.lastname: Allshire
authors.forename: Karl
authors.initials: K
authors.lastname: Ekwall
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002503:Centromere / Q000235:genetics*; D002842:Chromatids / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases; D006657:Histones / Q000378:metabolism; D009154:Mutation; D011233:Precipitin Tests; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C115303:Clr6 protein, S pombe; D006657:Histones; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D014157:Transcription Factors; C499368:pst1 protein, S pombe; D006655:Histone Deacetylases