Department of Chemical and Biological Physics, Weizmann Institute of Science, Rehovot, Israel.
PLoS Comput Biol. 2023 May 25;19(5):e1011142. doi: 10.1371/journal.pcbi.1011142. eCollection 2023 May.
Chromosomes are arranged in distinct territories within the nucleus of animal cells. Recent experiments have shown that these territories overlap at their edges, suggesting partial mixing during interphase. Experiments that knock-down of condensin II proteins during interphase indicate increased chromosome mixing, which demonstrates control of the mixing. In this study, we use a generic polymer simulation to quantify the dynamics of chromosome mixing over time. We introduce the chromosome mixing index, which quantifies the mixing of distinct chromosomes in the nucleus. We find that the chromosome mixing index in a small confinement volume (as a model of the nucleus), increases as a power-law of the time, with the scaling exponent varying non-monotonically with self-interaction and volume fraction. By comparing the chromosome mixing index with both monomer subdiffusion due to (non-topological) intermingling of chromosomes as well as even slower reptation, we show that for relatively large volume fractions, the scaling exponent of the chromosome mixing index is related to Rouse dynamics for relatively weak chromosome attractions and to reptation for strong attractions. In addition, we extend our model to more realistically account for the situation of the Drosophila chromosome by including the heterogeneity of the polymers and their lengths to account for microphase separation of euchromatin and heterochromatin and their interactions with the nuclear lamina. We find that the interaction with the lamina further impedes chromosome mixing.
染色体在动物细胞的细胞核中排列在不同的区域。最近的实验表明，这些区域在边缘处重叠，表明在间期存在部分混合。在间期敲低凝聚素 II 蛋白的实验表明，染色体混合增加，这表明了对混合的控制。在这项研究中，我们使用通用聚合物模拟来定量随时间变化的染色体混合动力学。我们引入了染色体混合指数，它量化了核内不同染色体的混合程度。我们发现，在小约束体积（作为细胞核的模型）中，染色体混合指数随时间呈幂律增加，标度指数随自相互作用和体积分数的变化而非单调变化。通过将染色体混合指数与由于染色体的（非拓扑）混合导致的单体亚扩散以及甚至更慢的蠕动进行比较，我们表明，对于相对较大的体积分数，染色体混合指数的标度指数与较弱染色体吸引力的 Rouse 动力学以及较强吸引力的蠕动有关。此外，我们通过包括聚合物的异质性及其长度来扩展我们的模型，以更真实地考虑果蝇染色体的情况，以解释常染色质和异染色质的微相分离及其与核纤层的相互作用。我们发现，与核纤层的相互作用进一步阻碍了染色体的混合。
