Abstract:
Many biomolecular condensates, including transcriptional condensates, are formed in elastic mediums. In this work, we study the nonequilibrium condensate dynamics in a chromatin-like environment modeled as a heterogeneous elastic medium. We demonstrate that the ripening process in such an elastic medium exhibits a temporal power-law scaling of the average condensate radius, depending on the local stiffness distribution and different from Ostwald ripening. Moreover, we incorporate an active process to model the dissolution of transcriptional condensates upon RNA accumulation. Intriguingly, three types of kinetics of condensate growth emerge, corresponding to constitutively expressed, transcriptional-bursting, and silenced genes. Furthermore, the simulated burst frequency decreases exponentially with the local stiffness, through which we infer a lognormal distribution of local stiffness in living cells using the transcriptome-wide distribution of burst frequency. Under the inferred stiffness distribution, the simulated distributions of bursting kinetic parameters agree reasonably well with the experimental data. Our findings reveal the interplay between biomolecular condensates and elastic mediums, yielding far-reaching implications for gene expression.
摘要:
许多生物分子缩合物,包括转录缩合物,在弹性介质中形成。在这项工作中,我们研究了模拟为非均质弹性介质的染色质样环境中的非平衡凝聚动力学。我们证明了在这种弹性介质中的成熟过程表现出平均冷凝半径的时间幂律标度,取决于局部刚度分布,与奥斯特瓦尔德熟化不同。此外,我们引入了一个主动过程来模拟RNA积累时转录缩合物的溶解。有趣的是,凝析油生长的三种类型的动力学出现,对应于组成型表达,转录爆发,和沉默的基因。此外,模拟突发频率随局部刚度呈指数下降,通过该方法,我们使用爆发频率的转录组范围分布来推断活细胞中局部刚度的对数正态分布。在推断的刚度分布下,爆破动力学参数的模拟分布与实验数据吻合较好。我们的发现揭示了生物分子缩合物和弹性介质之间的相互作用,对基因表达产生深远的影响。