<a href="https://ror.org/00sb7hc59">Max-Planck Institute for Polymer Research</a>, 55128 Mainz, Germany.
Department of Materials Science and Engineering, Department of Chemistry, Department of Chemical and Biological Engineering, and Department of Physics and Astronomy, <a href="https://ror.org/000e0be47">Northwestern University</a>, Evanston, Illinois 60208, USA.
Phys Rev E. 2024 Jul;110(1-1):014403. doi: 10.1103/PhysRevE.110.014403.
The highly and slightly condensed forms of chromatin, heterochromatin and euchromatin, respectively, segregate in the cell nucleus. Heterochromatin is more abundant in the nucleus periphery. Here we study the mechanism of heterochromatin segregation by modeling interphase chromosomes as diblock ring copolymers confined in a rigid spherical shell using molecular dynamics simulations. In our model, heterochromatin and euchromatin are distinguished by their bending stiffnesses only, while an interaction potential between the spherical shell and chromatin is used to model lamin-associated proteins. Our simulations indicate that in the absence of attractive interactions between the nuclear shell and the chromatin, most heterochromatin segregates towards the nuclear interior due to the depletion of less flexible heterochromatin segments from the nuclear periphery. This inverted chromatin distribution,which is opposite to the conventional case with heterochromatin dominating at the periphery, is in accord with experimental observations in rod cells. This "inversion" is also found to be independent of the heterochromatin concentration and chromosome number. The chromatin distribution at the periphery found in vivo can be recovered by further increasing the bending stiffness of heterochromatin segments or by turning on attractive interactions between the nuclear shell and heterochromatin. Our results indicate that the bending stiffness of chromatin could be a contributor to chromosome organization along with differential effects of HP1α-driven phase segregation and of loop extruders and interactions with the nuclear envelope and topological constraints.
高度浓缩和轻度浓缩的染色质分别为异染色质和常染色质，它们在细胞核中分离。异染色质在核周更丰富。在这里，我们通过使用分子动力学模拟将间期染色体建模为刚性球形壳中的两嵌段环共聚物，研究异染色质分离的机制。在我们的模型中，异染色质和常染色质仅通过其弯曲刚度来区分，而球形壳和染色质之间的相互作用势能用于模拟核纤层相关蛋白。我们的模拟表明，在核壳和染色质之间没有吸引力相互作用的情况下，由于较少柔性的异染色质片段从核周缘耗尽，大多数异染色质会向核内部分离。这种反转的染色质分布与传统的异染色质在外周占主导地位的情况相反，与杆状细胞的实验观察结果一致。这种“反转”也与异染色质浓度和染色体数目无关。通过进一步增加异染色质片段的弯曲刚度或打开核壳与异染色质之间的吸引力相互作用，可以恢复体内发现的周边染色质分布。我们的结果表明，染色质的弯曲刚度可能是染色体组织的一个贡献因素，同时还存在 HP1α 驱动的相分离以及环挤出器的差异效应，以及与核膜的相互作用和拓扑约束。
