title: γH2A is a component of yeast heterochromatin required for telomere elongation.
abstract: Histones of heterochromatin are deacetylated in yeast and methylated in more complex eukaryotes to regulate heterochromatin structure and gene silencing. Here, we report that histone H2A phosphorylated at serine 129 (γH2A) in Saccharomyces cerevisiae is a conceptually new type of heterochromatin modification that functions downstream of silent chromatin assembly. We show that γH2A is enriched throughout yeast telomeric and silent mating locus (HM) heterochromatin where γH2A results from the action of kinases Tel1 and Mec1. Interestingly, mutation of γH2A has no apparent effect on the binding of Sir (silent information regulator) complex or on gene silencing. In contrast, deletion of SIR3 abolishes the formation of γH2A at heterochromatin. To address the function of γH2A, we used a Δrif1 mutant strain in which telomeres are excessively elongated to show that γH2A is required for the optimal recruitment of Cdc13, a regulator of telomere elongation, and for telomere elongation itself. Thus, a histone modification that parallels Sir3 protein binding is shown here to be dispensable for the formation of a silent structure but is important for a crucial heterochromatin-specific downstream function in telomere homeostasis.
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kitada
authors.forename: Thomas
authors.initials: T
authors.lastname: Schleker
authors.forename: Adam S
authors.initials: AS
authors.lastname: Sperling
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
authors.forename: Michael
authors.initials: M
authors.lastname: Grunstein
mesh_terms: D002455:Cell Division; D047369:Chromatin Immunoprecipitation; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism* / Q000502:physiology; D034501:Telomere-Binding Proteins / Q000378:metabolism
chemical_list: C452219:Cdc13 protein, S cerevisiae; D006570:Heterochromatin; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D034501:Telomere-Binding Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae