title: Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity.
abstract: The post-translational modifications of histones are key to the modulation of chromatin structure. Distinct patterns of modifications established by histone-modifying enzymes control diverse chromosomal processes. Here, we report the purification and molecular characterization of the fission yeast Clr6 histone deacetyl ase involved in higher order chromatin assembly. We show that a chromodomain protein Alp13, which belongs to the conserved MRG protein family linked to cellular senescence in humans, is associated with Clr6. In addition, Clr6 interacts with homologs of the mammalian transcriptional co-repressors Sin3, Pst1 and Pst2, and a WD40 repeat-containing protein, Prw1. Alp13, Pst2 and Prw1 form a stable complex with Clr6 in the nucleus. Deletion of any of these factors causes progressive loss of viability and sensitivity to DNA-damaging agents, and impairs condensation/resolution of chromosomes during mitosis. This is accompanied by hyperacetylation of histones and a reduction in histone H3 Ser10 phosphorylation, which correlates with chromosome condensation during mitosis. These results link the MRG family protein Alp13 to histone deacetylation, and suggest that Clr6 and its associated factors are essential for fundamental chromosomal events.
authors.affiliation: Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, NY 11724, USA.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Nakayama
authors.forename: Guoping
authors.initials: G
authors.lastname: Xiao
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Noma
authors.forename: Asra
authors.initials: A
authors.lastname: Malikzay
authors.forename: Pernilla
authors.initials: P
authors.lastname: Bjerling
authors.forename: Karl
authors.initials: K
authors.lastname: Ekwall
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Shiv I S
authors.initials: SI
authors.lastname: Grewal
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016922:Cellular Senescence; D017124:Conserved Sequence; D017353:Gene Deletion; D016681:Genome, Fungal; D006655:Histone Deacetylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000737:chemistry
chemical_list: C475479:Alp13 protein, S pombe; D018797:Cell Cycle Proteins; C115303:Clr6 protein, S pombe; D006657:Histones; D010446:Peptide Fragments; D029702:Schizosaccharomyces pombe Proteins; D012694:Serine; D006655:Histone Deacetylases