Dipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy.
Berlin Institute for Medical Systems Biology, Max-Delbrück Centre (MDC) for Molecular Medicine, Berlin, Germany.
Biochem Soc Trans. 2021 Aug 27;49(4):1675-1684. doi: 10.1042/BST20201004.
The development of new experimental technologies is opening the way to a deeper investigation of the three-dimensional organization of chromosomes inside the cell nucleus. Genome architecture is linked to vital functional purposes, yet a full comprehension of the mechanisms behind DNA folding is still far from being accomplished. Theoretical approaches based on polymer physics have been employed to understand the complexity of chromatin architecture data and to unveil the basic mechanisms shaping its structure. Here, we review some recent advances in the field to discuss how Polymer Physics, combined with numerical Molecular Dynamics simulation and Machine Learning based inference, can capture important aspects of genome organization, including the description of tissue-specific structural rearrangements, the detection of novel, regulatory-linked architectural elements and the structural variability of chromatin at the single-cell level.
新实验技术的发展为深入研究细胞内染色体的三维组织开辟了道路。基因组结构与重要的功能目的相关联，但对 DNA 折叠背后的机制的全面理解仍远未完成。基于聚合物物理的理论方法已被用于理解染色质结构数据的复杂性，并揭示塑造其结构的基本机制。在这里，我们回顾该领域的一些最新进展，讨论聚合物物理如何结合数值分子动力学模拟和基于机器学习的推断，来捕捉基因组组织的重要方面，包括描述组织特异性结构重排、检测新的、与调控相关的结构元件以及单细胞水平上染色质的结构可变性。
