Abstract：
Genomic regions can acquire heritable epigenetic states through unique histone modifications, which lead to stable gene expression patterns without altering the underlying DNA sequence. However, the relationship between chromatin conformational dynamics and epigenetic stability is poorly understood. In this paper, we propose kinetic models to investigate the dynamic fluctuations of histone modifications and the spatial interactions between nucleosomes. Our model explicitly incorporates the influence of chemical modifications on the structural stability of chromatin and the contribution of chromatin contacts to the cooperative nature of chemical reactions. Through stochastic simulations and analytical theory, we have discovered distinct steady-state outcomes in different kinetic regimes, resembling a dynamical phase transition. Importantly, we have validated that the emergence of this transition, which occurs on biologically relevant timescales, is robust against variations in model design and parameters. Our findings suggest that the viscoelastic properties of chromatin and the timescale at which it transitions from a gel-like to a liquidlike state significantly impact dynamic processes that occur along the one-dimensional DNA sequence.
摘要：
基因组区域可以通过独特的组蛋白修饰获得可遗传的表观遗传状态，这导致稳定的基因表达模式，而不会改变潜在的DNA序列。然而,染色质构象动力学与表观遗传稳定性之间的关系尚不清楚。在本文中,我们提出了动力学模型来研究组蛋白修饰的动态波动和核小体之间的空间相互作用。我们的模型明确纳入了化学修饰对染色质结构稳定性的影响以及染色质接触对化学反应协同性质的贡献。通过随机模拟和分析理论，我们在不同的动力学状态下发现了不同的稳态结果，类似于动态相变。重要的是,我们已经验证了这种转变的出现，发生在生物学相关的时间尺度上，对模型设计和参数的变化具有鲁棒性。我们的发现表明，染色质的粘弹性特性及其从凝胶状状态转变为液状状态的时间尺度显着影响沿一维DNA序列发生的动态过程。
