title: The proper connection between shelterin components is required for telomeric heterochromatin assembly.
abstract: Telomeric regions contain prominent sites of heterochromatin, which is associated with unique histone modification profiles such as the methylation of histone H3 at Lys9 (H3K9me). In fission yeast, the conserved telomeric shelterin complex recruits the histone H3K9 methyltransferase complex CLRC to establish subtelomeric heterochromatin. Although many shelterin mutations affect subtelomeric heterochromatin assembly, the mechanism remains elusive due to the diverse functions of shelterin. Through affinity purification, we found that shelterin directly associates with CLRC through the Ccq1 subunit. Surprisingly, mutations that disrupt interactions between shelterin subunits compromise subtelomeric heterochromatin without affecting CLRC interaction with shelterin component Pot1, located at chromosome ends. We further discovered that telomeric repeats are refractory to heterochromatin spreading and that artificial restoration of shelterin connections or increased heterochromatin spreading rescued heterochromatin defects in these shelterin mutants. Thus, subtelomeric heterochromatin assembly requires both the recruitment of CLRC by shelterin to chromosome ends and the proper connection of shelterin components, which allows CLRC to skip telomeric repeats to internal regions.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA;
authors.forename: Jiyong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA;
authors.forename: Allison L
authors.initials: AL
authors.lastname: Cohen
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA;
authors.forename: Anudari
authors.initials: A
authors.lastname: Letian
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA;
authors.forename: Xavier
authors.initials: X
authors.lastname: Tadeo
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA;
authors.forename: James J
authors.initials: JJ
authors.lastname: Moresco
authors.affiliation: Department of Biological Chemistry, University of California at Irvine, Irvine, California 92697, USA.
authors.forename: Jinqiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA;
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Biological Chemistry, University of California at Irvine, Irvine, California 92697, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiao
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA;
authors.forename: Songtao
authors.initials: S
authors.lastname: Jia
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D000089804:Shelterin Complex; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C529647:Ccq1 protein, S pombe; D006570:Heterochromatin; D029702:Schizosaccharomyces pombe Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C499082:pot1 protein, S pombe; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase
keywords: heterochromatin; shelterin; spreading; telomere