Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo , Oslo, Norway.
Laboratoire De Physique Théorique, IRSAMC, Université De Toulouse (UPS) , CNRS, Toulouse, France.
Nucleus. 2021 Dec;12(1):6-20. doi: 10.1080/19491034.2020.1868105.
Interactions of chromatin with the nuclear lamina imposes a radial genome distribution important for nuclear functions. How physical properties of chromatin affect these interactions is unclear. We used polymer simulations to model how physical parameters of chromatin affect its interaction with the lamina. Impact of polymer stiffness is greater than stretching on its configurations at the lamina; these are manifested as trains describing extended interactions, and loops describing desorbed regions . Conferring an attraction potential leads to persistent interaction and adsorption-desorption regimes manifested by fluctuations between trains and loops. These are modulated by polymer stiffness and stretching, with a dominant impact of stiffness on resulting structural configurations. We infer that flexible euchromatin is more prone to stochastic interactions with lamins than rigid heterochromatin characterizing constitutive LADs. Our models provide insights on the physical properties of chromatin as a polymer which affect the dynamics and patterns of interactions with the nuclear lamina.
染色质与核纤层的相互作用施加了一个径向的基因组分布,这对核功能很重要。染色质的物理性质如何影响这些相互作用尚不清楚。我们使用聚合物模拟来模拟染色质的物理参数如何影响其与纤层的相互作用。聚合物的刚性比拉伸对其在纤层上的构象的影响更大;这些表现为描述扩展相互作用的列车,以及描述解吸区域的环。赋予吸引势能会导致持久的相互作用和吸附-解吸状态,表现为列车和环之间的波动。这些波动受聚合物的刚性和拉伸的调节,刚性对最终结构构象有主要影响。我们推断,与组成性 LAD 所具有的刚性异染色质相比,柔性常染色质更容易与核纤层发生随机相互作用。我们的模型提供了关于作为聚合物的染色质的物理性质的见解,这些性质会影响与核纤层相互作用的动力学和模式。