Spatial reorganization of telomeres in long-lived quiescent cells.
Spatial reorganization of telomeres in long-lived quiescent cells.
复制标题
DOI：
10.1186/s13059-015-0766-2
复制
发表时间：
2015-09-23
期刊：
影响因子：
12.3
通讯作者：
Taddei A
中科院分区：
文献类型：
--
作者：
Guidi M;Ruault M;Marbouty M;Loïodice I;Cournac A;Billaudeau C;Hocher A;Mozziconacci J;Koszul R;Taddei A
染色质的时空行为是基因组功能的重要调控机制。在酿酒酵母中的研究已经广泛地证明了核组织的功能重要性。虽然野生酵母的存活取决于它们抵御不利条件的能力，但大多数研究都是在经历指数生长的细胞上进行的。在这些条件下，在大多数真核细胞中，主要在32个端粒处发现的沉默染色质在核膜处积累，形成三到五个焦点。在这里，结合活显微镜，DNA FISH和染色体构象捕获（HiC）技术，我们报告说，染色体采用不同的组织根据细胞的代谢状态。特别是，在碳源耗尽后，长寿命的静止细胞的基因组经历了由端粒分组成位于细胞核中心的独特焦点或超簇驱动的重大空间重组。基因组构象的这种变化是能够维持长期生存能力的静止细胞所特有的。我们进一步表明，在呼吸过程中线粒体活动产生的活性氧使细胞在饥饿时形成超簇。重要的是，删除编码端粒相关沉默因子SIR 3的基因消除了端粒分组并降低了寿命，这是一种通过表达能够形成超簇的沉默缺陷SIR 3等位基因而挽救的缺陷。我们的数据表明，线粒体活性引发细胞在饥饿时将其端粒分组为超簇，将基因组结构重塑为可能有助于维持静止细胞寿命的构象。本文的在线版本（doi：10.1186/s13059-015-0766-2）包含补充材料，可供授权用户使用。
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. 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. 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. The online version of this article (doi:10.1186/s13059-015-0766-2) contains supplementary material, which is available to authorized users.