Spatial reorganization of telomeres in long-lived quiescent cells

Abstract

BackgroundThe 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.ResultsHere, 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.ConclusionsOur 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 materialThe online version of this article (doi:10.1186/s13059-015-0766-2) contains supplementary material, which is available to authorized users.

Cohesins and condensins orchestrate the 4D dynamics of yeast chromosomes during the cell cycle

“…Cells were grown at either 30°C or 23–25°C (the later temperature corresponding to the permissive temperature of the conditional thermosensitive mutations cdc6‐1 , cdc14‐3 , and cdc15‐2 ; see below for details). Dataset corresponding to the quiescent state (G0) comes from already published data by Guidi et al (2015) and was obtained by carbon source exhaustion. All strains are described in Table EV1.…”

“…However, the initiation and progression of replication, followed by the segregation of the sister chromatids (SCs) into daughter cells, is expected to modify the genome higher‐order organization. Recent studies have unveiled cell‐cycle stage‐specific genome‐wide topological variations in bacteria, yeast, fly, and mammals (Naumova et al , 2013; Guidi et al , 2015; Marbouty et al , 2015; Hug et al , 2017). As expected, in all species the largest reorganization transition is associated with SC condensation, a fundamental process occurring concomitantly to their individualization, and facilitating their proper segregation.…”

SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

“…Further experiments assessing whether SMARCA4 affects nucleosome positioning at or enhances/interferes with binding of specific proteins at telomeres to affect higher-order telomeric structures will shed further light on the relationship between SMARCA4 and telomere organization. Recently, Guidi et al (2015) showed that the telomeres of yeast cells undergo spatial reorganization upon switching to different metabolic states. Because our RNA-seq analysis showed up-regulation of genes related to lipid synthesis and since our Hi-C analysis showed alterations in telomeric interactions in shSMARCA4 cells, it is tempting to speculate that the increased telomeric interactions (Fig.…”

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

“…Telomeres at the ends of chromosome arms of similar length associate with one another more frequently, owing to the comigration of centromeres at anaphase (Schober et al 2008;Therizols et al 2010). Interestingly, long-lived stationary-phase cells group all telomeres into a single Sir3-dependent cluster, a genomic restructuring event that extends chronological life span (Guidi et al 2015).…”

“…Kamakaka and colleagues suggested that DNA-repair proteins and DNA homology contribute to long-range interactions between the HM loci (Kirkland and Kamakaka 2013). More generally, interactions between the subtelomeric silent chromatin of different chromosomes are driven by self-association of Sir3 and are independent of DNA homology (Ruault et al 2011;Guidi et al 2015). At high concentrations, pure Sir3 causes nucleosome arrays to condense and aggregate (McBryant et al 2008;Swygert et al 2014).…”