Several mechanisms directing a rapid transcriptional reactivation of genes immediately after mitosis have been described. However, little is known about the maintenance of repressive signals during mitosis. In this work, we address the role of Ski in the repression of gene expression during M/G1 transition in mouse embryonic fibroblasts (MEFs). We found that Ski localises as a distinct pair of dots at the pericentromeric region of mitotic chromosomes, and the absence of the protein is related to high acetylation and low tri-methylation of H3K9 in pericentromeric major satellite. Moreover, differential expression assays in early G1 cells showed that the presence of Ski is significantly associated with repression of genes localised nearby to pericentromeric DNA. In mitotic cells, chromatin immunoprecipitation assays confirmed the association of Ski to major satellite and the promoters of the most repressed genes: Mmp3, Mmp10 and Mmp13. These genes are at pericentromeric region of chromosome 9. In these promoters, the presence of Ski resulted in increased H3K9 tri-methylation levels. This Ski-dependent regulation is also observed during interphase. Consequently, Mmp activity is augmented in Ski-/- MEFs. Altogether, these data indicate that association of Ski with the pericentromeric region of chromosomes during mitosis is required to maintain the silencing bookmarks of underlying chromatin.

中文翻译：

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在主要卫星中，H3K9的三甲基化作用和小鼠成纤维细胞中的环变异构体​​基因Mmp3，Mmp10和Mmp13的抑制都需要使用滑雪板。

已经描述了在有丝分裂后立即指导基因快速转录重新激活的几种机制。但是，关于在有丝分裂期间维持抑制信号知之甚少。在这项工作中，我们解决了Ski在小鼠胚胎成纤维细胞（MEFs）的M / G1过渡过程中抑制基因表达的作用。我们发现Ski定位为有丝分裂染色体的着丝粒区域附近的一对独特的点，并且该蛋白质的缺失与着丝粒主要卫星中H3K9的高乙酰化和低三甲基化有关。此外，早期G1细胞中的差异表达分析表明，Ski的存在与抑制围绕着着丝粒的DNA定位的基因显着相关。在有丝分裂细胞中 染色质免疫沉淀测定法证实了Ski与主要卫星以及最受抑制的基因Mmp3，Mmp10和Mmp13的启动子有关。这些基因位于9号染色体的着丝粒区域。在这些启动子中，Ski的存在导致H3K9三甲基化水平提高。在相间期也观察到这种与滑雪有关的调节。因此，Ski-/-MEF中的Mmp活动得以增强。总而言之，这些数据表明在有丝分裂过程中需要将Ski与染色体的着丝粒区域结合起来，以保持潜在染色质的沉默。在相间期也观察到这种与滑雪有关的调节。因此，Ski-/-MEF中的Mmp活动得以增强。总而言之，这些数据表明在有丝分裂期间，Ski与染色体的着丝粒区域的关联是维持潜在染色质的沉默书签所必需的。在相间期也观察到这种与滑雪有关的调节。因此，Ski-/-MEF中的Mmp活动得以增强。总而言之，这些数据表明在有丝分裂期间，Ski与染色体的着丝粒区域的关联是维持潜在染色质的沉默书签所必需的。