论文标题
聚合物建模预测衰老的染色体重组
Polymer Modelling Predicts Chromosome Reorganisation in Senescence
论文作者
论文摘要
层层相关域（LAD）覆盖了人类基因组的很大一部分，被认为在塑造核建筑景观方面起着重要作用。在这里，我们执行聚合物模拟，显微镜和质谱法，以剖析核组织中异染色质和椎板介导的相互作用的作用。我们的模型解释了生长细胞中异染色质和白染色质的常规组织以及在癌基因诱导的衰老和后代中发现的病理组织。我们表明，通过系统中的相变，可以将实验观察到的衰变和雌不同细胞的接触位置的变化解释为引起。在我们的模拟中，就像实验一样，LAD是高度随机的。我们的模型表明，一旦确定，即使恢复了薄片介导的相互作用，衰老表型也应该是可稳定的。总体而言，我们的模拟发现了一种通用物理机制，该机制可以调节多种哺乳动物核的异染色质分离和LAD形成。
Lamina-associated domains (LADs) cover a large part of the human genome and are thought to play a major role in shaping the nuclear architectural landscape. Here, we perform polymer simulations, microscopy and mass spectrometry to dissect the roles played by heterochromatin- and lamina-mediated interactions in nuclear organisation. Our model explains the conventional organisation of heterochromatin and euchromatin in growing cells and the pathological organisation found in oncogene-induced senescence and progeria. We show that the experimentally observed changes in the locality of contacts in senescent and progeroid cells can be explained as arising due to phase transitions in the system. Within our simulations LADs are highly stochastic, as in experiments. Our model suggests that, once established, the senescent phenotype should be metastable even if lamina-mediated interactions were reinstated. Overall, our simulations uncover a generic physical mechanism that can regulate heterochromatin segregation and LAD formation in a wide range of mammalian nuclei.
