Cheng Tammy M K, Heeger Sebastian, Chaleil Raphaël A G, Matthews Nik, Stewart Aengus, Wright Jon, Lim Carmay, Bates Paul A, Uhlmann Frank
Biomolecular Modelling Laboratory, Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, United Kingdom.
Chromosome Segregation Laboratory, Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, United Kingdom.
Elife. 2015 Apr 29;4:e05565. doi: 10.7554/eLife.05565.
Mitotic chromosomes were one of the first cell biological structures to be described, yet their molecular architecture remains poorly understood. We have devised a simple biophysical model of a 300 kb-long nucleosome chain, the size of a budding yeast chromosome, constrained by interactions between binding sites of the chromosomal condensin complex, a key component of interphase and mitotic chromosomes. Comparisons of computational and experimental (4C) interaction maps, and other biophysical features, allow us to predict a mode of condensin action. Stochastic condensin-mediated pairwise interactions along the nucleosome chain generate native-like chromosome features and recapitulate chromosome compaction and individualization during mitotic condensation. Higher order interactions between condensin binding sites explain the data less well. Our results suggest that basic assumptions about chromatin behavior go a long way to explain chromosome architecture and are able to generate a molecular model of what the inside of a chromosome is likely to look like.
有丝分裂染色体是最早被描述的细胞生物学结构之一,但其分子结构仍知之甚少。我们设计了一个简单的生物物理模型,模拟一条300 kb长的核小体链,其大小与出芽酵母染色体相当,该模型受染色体凝聚素复合体(间期和有丝分裂染色体的关键组成部分)结合位点之间的相互作用所约束。通过比较计算和实验(4C)相互作用图谱以及其他生物物理特征,我们能够预测凝聚素的作用模式。沿着核小体链随机发生的由凝聚素介导的成对相互作用产生了类似天然染色体的特征,并概括了有丝分裂凝聚过程中染色体的压缩和个体化。凝聚素结合位点之间的高阶相互作用对数据的解释效果较差。我们的结果表明,关于染色质行为的基本假设在很大程度上有助于解释染色体结构,并能够生成一个关于染色体内部可能样子的分子模型。