论文标题
相分离与基因增强器交流之间的相互作用：一项理论研究
The interplay between phase-separation and gene-enhancer communication: a theoretical study
论文作者
论文摘要
在这里研究了在相互相互作用的蛋白质系统中发生的相分离化，该系统可以在染色质纤维的特定位点结合。这是通过简单聚合物模型的广泛分子动力学模拟来实现的，该模型包括调节蛋白作为相互作用的球形颗粒。我们的兴趣尤其集中在相分离在形成分子聚集体中所起的作用，这些分子聚集体可以沿DNA连接远处的调节元件，例如基因启动子和增强子。我们发现，在依赖于分子浓度，分子 - 摩尔分子和分子-DNA相互作用的适当条件下，由结合分子和染色质素之间的相互相互作用产生的系统的总体平衡状态可以导致相位分离的分子簇的形成，从而可以在调节位点之间进行鲁棒接触。反之亦然，调节位点的存在可以促进相分离过程。不同的动力学机制可以通过结合位点的簇成核或通过逐渐吸引结合位点的介导簇的大量自发形成来产生增强子促进剂的接触。还讨论了此类过程可以解释在时间期间调节位点之间实验性的活细胞成像数据测量距离的可能性。
The phase-separation occurring in a system of mutually interacting proteins that can bind on specific sites of a chromatin fiber is here investigated. This is achieved by means of extensive Molecular Dynamics simulations of a simple polymer model which includes regulatory proteins as interacting spherical particles. Our interest is particularly focused on the role played by phase-separation in the formation of molecule aggregates that can join distant regulatory elements, such as gene promoters and enhancers, along the DNA. We find that the overall equilibrium state of the system resulting from the mutual interplay between binding molecules and chromatin can lead, under suitable conditions that depend on molecules concentration, molecule-molecule and molecule-DNA interactions, to the formation of phase-separated molecular clusters allowing robust contacts between regulatory sites. Vice-versa, the presence of regulatory sites can promote the phase-separation process. Different dynamical regimes can generate the enhancer-promoter contact, either by cluster nucleation at binding sites or by bulk spontaneous formation of the mediating cluster to which binding sites are successively attracted. The possibility that such processes can explain experimental live-cell imaging data measuring distances between regulatory sites during time is also discussed.
