While there is a prevalent genome organization in eukaryotic cells, with heterochromatin concentrated at the nuclear periphery, anomalous cases do occur. Deviations of chromatin distribution are frequent, for example, upon aging, under malignant diseases, or even naturally in rod cells of nocturnal mammals. Using molecular dynamic simulations, we study the segregation of heterochromatin in the cell nucleus by modeling interphase chromosomes as diblock ring copolymers confined in a rigid spherical shell. In our model, heterochromatin and euchromatin are distinguished by their bending stiffnesses, while an interaction potential between the spherical shell and chromatin is used as a proxy for lamin-associated proteins. Our simulations indicate that in the absence of attractive interactions between the nuclear shell and the chromatin, the majority of heterochromatin segregates towards the nuclear interior due to depletion of less flexible heterochromatin segments from the nuclear periphery. This inverted chromatin distribution is in accord with experimental observations in rod cells. This "inversion" is also found to be independent of the heterochromatin concentration and chromosome number, and is further enhanced by additional attractive interactions between heterochromatin segments. as well as by allowing bond-crossing to emulate topoisomerase activity. The usual chromatin distribution, with heterochromatin at the periphery, can be recovered by further increasing the bending stiffness of heterochromatin segments or by turning on attractive interactions between the nuclear shell and heterochromatin. Overall, our results indicate that 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.

中文翻译：

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异染色质柔韧性有助于细胞核中的染色体分离

尽管真核细胞中存在普遍的基因组组织，异染色质集中在核外围，但确实发生异常情况。染色质分布的偏差是经常发生的，例如，在衰老，恶性疾病下，甚至在夜间哺乳动物的杆状细胞中自然发生。使用分子动力学模拟，我们通过将相间染色体建模为封闭在刚性球形壳中的二嵌段环共聚物，研究了异染色质在细胞核中的分离。在我们的模型中，异染色质和常染色质的弯曲刚度是不同的，而球形壳和染色质之间的相互作用势则可作为层粘连蛋白的替代物。我们的模拟表明，在核壳与染色质之间不存在有吸引力的相互作用的情况下，由于缺乏弹性的异染色质片段从核外围耗尽，大多数异染色质向核内部隔离。这种反向的染色质分布与杆状细胞中的实验观察一致。还发现这种“倒置”与异染色质浓度和染色体数目无关，并且通过异染色质片段之间的其他吸引相互作用进一步增强。以及通过允许键交叉模拟拓扑异构酶活性。可以通过进一步增加异染色质片段的弯曲刚度或通过打开核壳与异染色质之间的有吸引力的相互作用来恢复通常的染色质分布，在外围具有异染色质。总体，