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Shelterin and subtelomeric DNA sequences control nucleosome maintenance and genome stability
Author(s) -
Emden Thomas S,
Forn Marta,
Forné Ignasi,
Sarkadi Zsuzsa,
Capella Matías,
Martín Caballero Lucía,
FischerBurkart Sabine,
Brönner Cornelia,
Simonetta Marco,
Toczyski David,
Halic Mario,
Imhof Axel,
Braun Sigurd
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201847181
Subject(s) - dna , nucleosome , genome , shelterin , biology , genetics , telomere , whole genome sequencing , computational biology , dna binding protein , gene , histone , transcription factor
Telomeres and the shelterin complex cap and protect the ends of chromosomes. Telomeres are flanked by the subtelomeric sequences that have also been implicated in telomere regulation, although their role is not well defined. Here, we show that, in Schizosaccharomyces pombe , the telomere‐associated sequences ( TAS ) present on most subtelomeres are hyper‐recombinogenic, have metastable nucleosomes, and unusual low levels of H3K9 methylation. Ccq1, a subunit of shelterin, protects TAS from nucleosome loss by recruiting the heterochromatic repressor complexes CLRC and SHREC , thereby linking nucleosome stability to gene silencing. Nucleosome instability at TAS is independent of telomeric repeats and can be transmitted to an intrachromosomal locus containing an ectopic TAS fragment, indicating that this is an intrinsic property of the underlying DNA sequence. When telomerase recruitment is compromised in cells lacking Ccq1, DNA sequences present in the TAS promote recombination between chromosomal ends, independent of nucleosome abundance, implying an active function of these sequences in telomere maintenance. We propose that Ccq1 and fragile subtelomeres co‐evolved to regulate telomere plasticity by controlling nucleosome occupancy and genome stability.