Spatial reorganization of telomeres in long-lived quiescent cells

Autor: Angela Taddei, Antoine Hocher, Romain Koszul, Julien Mozziconacci, Martial Marbouty, Axel Cournac, Cyrille Billaudeau, Myriam Ruault, Micol Guidi, Isabelle Loïodice
Přispěvatelé: Dynamique du noyau, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique des génomes - Genetics of Genomes (UMR 3525), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Laboratoire de Physique Théorique de la Matière Condensée (LPTMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Genome Biology
Genome Biology, 2015, 16 (1), pp.206. ⟨10.1186/s13059-015-0766-2⟩
Genome Biology, BioMed Central, 2015, 16 (1), pp.206. ⟨10.1186/s13059-015-0766-2⟩
ISSN: 1465-6906
1474-760X
DOI: 10.1186/s13059-015-0766-2⟩
Popis: Background The spatiotemporal behavior of chromatin is an important control mechanism of genomic function. Studies in Saccharomyces cerevisiae have broadly contributed to demonstrate the functional importance of nuclear organization. Although in the wild yeast survival depends on their ability to withstand adverse conditions, most of these studies were conducted on cells undergoing exponential growth. In these conditions, as in most eukaryotic cells, silent chromatin that is mainly found at the 32 telomeres accumulates at the nuclear envelope, forming three to five foci. Results Here, combining live microscopy, DNA FISH and chromosome conformation capture (HiC) techniques, we report that chromosomes adopt distinct organizations according to the metabolic status of the cell. In particular, following carbon source exhaustion the genome of long-lived quiescent cells undergoes a major spatial re-organization driven by the grouping of telomeres into a unique focus or hypercluster localized in the center of the nucleus. This change in genome conformation is specific to quiescent cells able to sustain long-term viability. We further show that reactive oxygen species produced by mitochondrial activity during respiration commit the cell to form a hypercluster upon starvation. Importantly, deleting the gene encoding telomere associated silencing factor SIR3 abolishes telomere grouping and decreases longevity, a defect that is rescued by expressing a silencing defective SIR3 allele competent for hypercluster formation. Conclusions Our data show that mitochondrial activity primes cells to group their telomeres into a hypercluster upon starvation, reshaping the genome architecture into a conformation that may contribute to maintain longevity of quiescent cells. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0766-2) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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