Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871, China.
Proc Natl Acad Sci U S A. 2024 Mar 19;121(12):e2316610121. doi: 10.1073/pnas.2316610121. Epub 2024 Mar 15.
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.
许多生物分子凝聚物，包括转录凝聚物，都是在弹性介质中形成的。在这项工作中，我们研究了类似染色质的环境中的非平衡凝聚物动力学，该环境被建模为非均匀弹性介质。我们证明，在这种弹性介质中，老化过程表现出平均凝聚物半径的时间幂律标度，这取决于局部刚度分布，与奥斯特瓦尔德老化不同。此外，我们引入了一个主动过程来模拟 RNA 积累时转录凝聚物的溶解。有趣的是，三种凝聚物生长动力学类型出现，对应于组成型表达、转录爆发和沉默基因。此外，通过模拟，凝聚物的爆发频率随局部刚度呈指数衰减，由此我们使用全转录组的爆发频率分布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，模拟的爆发动力学参数分布与实验数据相当吻合。我们的发现揭示了生物分子凝聚物和弹性介质之间的相互作用，对基因表达产生了深远的影响。
