Center for Theoretical Biological Physics, Rice University, Houston, TX 77005;
Department of Chemistry, Iowa State University, Ames, IA 50011.
Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):7753-7758. doi: 10.1073/pnas.1806297115. Epub 2018 Jul 9.
The nucleus of a eukaryotic cell is a nonequilibrium system where chromatin is subjected to active processes that continuously rearrange it over the cell's life cycle. Tracking the motion of chromosomal loci provides information about the organization of the genome and the physical processes shaping that organization. Optical experiments report that loci move with subdiffusive dynamics and that there is spatially coherent motion of the chromatin. We recently showed that it is possible to predict the 3D architecture of genomes through a physical model for chromosomes that accounts for the biochemical interactions mediated by proteins and regulated by epigenetic markers through a transferable energy landscape. Here, we study the temporal dynamics generated by this quasi-equilibrium energy landscape assuming Langevin dynamics at an effective temperature. Using molecular dynamics simulations of two interacting human chromosomes, we show that the very same interactions that account for genome architecture naturally reproduce the spatial coherence, viscoelasticity, and the subdiffusive behavior of the motion in interphase chromosomes as observed in numerous experiments. The agreement between theory and experiments suggests that even if active processes are involved, an effective quasi-equilibrium landscape model can largely mimic their dynamical effects.
真核细胞的核是一个非平衡系统，其中染色质受到主动过程的影响，这些过程会在细胞的生命周期中不断地对其进行重组。跟踪染色体位置的运动提供了有关基因组组织和塑造该组织的物理过程的信息。光学实验报告说，位点以亚扩散动力学移动，并且染色质存在空间相干运动。我们最近表明，通过考虑由蛋白质介导的生化相互作用并通过可转移的能量景观由表观遗传标记调节的染色体的物理模型，有可能预测基因组的 3D 结构。在这里，我们研究了假定有效温度下的 Langevin动力学产生的准平衡能量景观的时间动力学。使用两个相互作用的人类染色体的分子动力学模拟，我们表明，解释基因组结构的相同相互作用自然地再现了空间相干性、粘弹性以及在众多实验中观察到的有丝分裂染色体运动的亚扩散行为。理论与实验之间的一致性表明，即使涉及主动过程，有效的准平衡景观模型也可以在很大程度上模拟其动力学效应。
