Université de Lyon, ENS de Lyon, Univ Claude Bernard, CNRS, Laboratoire de Biologie et Modélisation de la Cellule, 69007 Lyon, France.
CNAG-CRG, The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.
Genome Res. 2022 Jan;32(1):28-43. doi: 10.1101/gr.275827.121. Epub 2021 Dec 28.
Chromosome organization and dynamics are involved in regulating many fundamental processes such as gene transcription and DNA repair. Experiments unveiled that chromatin motion is highly heterogeneous inside cell nuclei, ranging from a liquid-like, mobile state to a gel-like, rigid regime. Using polymer modeling, we investigate how these different physical states and dynamical heterogeneities may emerge from the same structural mechanisms. We found that the formation of topologically associating domains (TADs) is a key driver of chromatin motion heterogeneity. In particular, we showed that the local degree of compaction of the TAD regulates the transition from a weakly compact, fluid state of chromatin to a more compact, gel state exhibiting anomalous diffusion and coherent motion. Our work provides a comprehensive study of chromosome dynamics and a unified view of chromatin motion enabling interpretation of the wide variety of dynamical behaviors observed experimentally across different biological conditions, suggesting that the "liquid" or "solid" state of chromatin are in fact two sides of the same coin.
染色体的组织和动态变化参与调控多种基本过程，如基因转录和 DNA 修复。实验揭示了细胞核内染色质的运动具有高度的异质性，从类似液体的、可移动的状态到类似凝胶的、刚性的状态。我们使用聚合物模型研究了这些不同的物理状态和动力学异质性如何可能源于相同的结构机制。我们发现拓扑关联域（TAD）的形成是染色质运动异质性的关键驱动因素。具体来说，我们表明 TAD 的局部紧致程度调节了染色质从弱紧致、流体状态到更紧致、凝胶状态的转变，凝胶状态表现出异常扩散和相干运动。我们的工作提供了对染色体动力学的全面研究和对染色质运动的统一观点，能够解释在不同生物条件下实验中观察到的广泛的动力学行为，表明染色质的“液体”或“固体”状态实际上是同一枚硬币的两面。
