Rouches Mason N, Machta Benjamin B
Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, Connecticut; Quantitative Biology Institute, Yale University, New Haven, Connecticut; Department of Physics, University of Chicago, Chicago, Illinois.
Quantitative Biology Institute, Yale University, New Haven, Connecticut; Department of Physics, Yale University, New Haven, Connecticut.
Biophys J. 2025 Jun 4. doi: 10.1016/j.bpj.2025.05.031.
The three-dimensional organization of chromatin is thought to play an important role in controlling gene expression. Specificity in expression is achieved through the interaction of transcription factors and other nuclear proteins with particular sequences of DNA. At unphysiological concentrations, many of these nuclear proteins can phase separate in the absence of DNA. In vivo, the thermodynamic forces driving these phases lead the chromosome to co-condense with nuclear proteins. However, it is unclear how DNA, itself a long polymer subject to configurational transitions, interacts with three-dimensional protein phases. Here, we show that a long compressible polymer can be coupled to interacting protein mixtures, leading to a generalized prewetting transition where polymer collapse is coincident with a locally stabilized liquid droplet. We use lattice Monte-Carlo simulations and a mean-field theory to show that these phases can be stable even in regimes where both polymer collapse and coexisting liquid phases are unstable in isolation and that these new transitions can be either abrupt or continuous. For polymers with internal linear structure, we further show that changes in the concentration of bulk components can lead to changes in three-dimensional polymer structure. In the nucleus, there are many distinct proteins that interact with many different regions of chromatin, potentially giving rise to many different prewet phases. The simple systems we consider here highlight chromatin's role as a lower-dimensional surface whose interactions with proteins are required for these novel phases.
染色质的三维结构被认为在控制基因表达中起着重要作用。通过转录因子和其他核蛋白与特定DNA序列的相互作用实现表达的特异性。在非生理浓度下，许多这些核蛋白在没有DNA的情况下会发生相分离。在体内，驱动这些相的热力学力导致染色体与核蛋白共同凝聚。然而，尚不清楚本身作为一种经历构象转变的长聚合物的DNA如何与三维蛋白质相相互作用。在这里，我们表明一种长的可压缩聚合物可以与相互作用的蛋白质混合物耦合，导致一种广义的预润湿转变，其中聚合物塌陷与局部稳定的液滴同时发生。我们使用晶格蒙特卡罗模拟和平均场理论表明，即使在聚合物塌陷和共存液相单独存在时不稳定的区域，这些相也可以是稳定的，并且这些新的转变可以是突然的或连续的。对于具有内部线性结构的聚合物，我们进一步表明本体组分浓度的变化会导致三维聚合物结构的变化。在细胞核中，有许多不同的蛋白质与染色质的许多不同区域相互作用，可能产生许多不同的预湿相。我们在此考虑的简单系统突出了染色质作为低维表面的作用，其与蛋白质的相互作用是这些新相所必需的。
