The proper connection between shelterin components is required for telomeric heterochromatin assembly
Autor: | Allison Cohen, Jiyong Wang, Jinqiang Liu, Feng Qiao, John R. Yates, Xavier Tadeo, James J. Moresco, Songtao Jia, Anudari Letian |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Heterochromatin Telomere-Binding Proteins Medical and Health Sciences Shelterin Complex 03 medical and health sciences Histone H3 Schizosaccharomyces Genetics telomere Telomeric heterochromatin assembly biology Methyltransferase complex Psychology and Cognitive Sciences heterochromatin Histone-Lysine N-Methyltransferase Telomere Biological Sciences Chromatin Assembly and Disassembly Shelterin Subtelomeric heterochromatin 030104 developmental biology Histone Mutation Histone Methyltransferases biology.protein Schizosaccharomyces pombe Proteins spreading Research Paper Protein Binding shelterin Developmental Biology |
Zdroj: | Genes & development, vol 30, iss 7 |
ISSN: | 1549-5477 0890-9369 |
Popis: | 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. |
Databáze: | OpenAIRE |
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