异质相互作用与聚合物熵决定染色质结构域的组织和动力学
Heterogeneous interactions and polymer entropy decide organization and dynamics of chromatin domains
AI总结：
本文利用实验接触图谱推导染色质片段相互作用强度，模拟人类染色体结构域的三维组织与动力学，揭示异质弱相互作用及聚合物熵对其时空性质、固液特征和环稳定的决定作用。
摘要：
已知染色质被组织成多个大小和压缩程度各异的结构域。虽然这些结构域常被设想为静态结构，但它们具有高度动态性，并表现出细胞间差异。由于基因调控和DNA复制等过程都发生在这些结构域的背景下，因此理解其组织、涨落和动力学十分重要。为模拟染色质结构域，需要了解染色质片段之间的相互作用强度。本文从实验已知的接触图谱中推导相互作用强度参数，并用其预测染色质的组织和动力学。以人类染色体上的两个结构域为例，研究其三维组织、尺寸/形状涨落以及一个结构域内不同片段的动力学，并考虑流体动力学效应。针对不同细胞类型，本文量化不同表观遗传状态下相互作用强度和染色质形状涨落的变化。通过系统地扰动相互作用强度，进一步研究类表观遗传变化如何改变结构域的时空性质。结果表明，异质弱相互作用对决定结构域的组织至关重要。通过计算有效刚度和弛豫时间，研究相互作用扰动如何影响染色质结构域的类固体和类液体性质。通过量化结构域内染色质片段的动力学，本文展示聚合物熵与相互作用能之间的竞争如何影响环形成的时间尺度以及稳定环的维持。
英文摘要：
Chromatin is known to be organized into multiple domains of varying sizes and compaction. While these domains are often imagined as static structures, they are highly dynamic and show cell-to-cell variability. Since processes such as gene regulation and DNA replication occur in the context of these domains, it is important to understand their organization, fluctuation and dynamics. To simulate chromatin domains, one requires knowledge of interaction strengths among chromatin segments. Here, we derive interaction strength parameters from experimentally known contact maps and use them to predict chromatin organization and dynamics. Taking two domains on the human chromosome as examples, we investigate its 3D organization, size/shape fluctuations, and dynamics of different segments within a domain, accounting for hydrodynamic effects. Considering different cell types, we quantify changes in interaction strengths and chromatin shape fluctuations in different epigenetic states. Perturbing the interaction strengths systematically, we further investigate how epigenetic-like changes can alter the spatio-temporal nature of the domains. Our results show that heterogeneous weak interactions are crucial in determining the organization of the domains. Computing effective stiffness and relaxation times, we investigate how perturbations in interactions affect the solid-like and liquid-like nature of chromatin domains. Quantifying dynamics of chromatin segments within a domain, we show how the competition between polymer entropy and interaction energy influence the timescales of loop formation and maintenance of stable loops.
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