Biophysics Program, Biochemistry Department, Stanford University, Stanford, California, USA.
Biophys J. 2010 Dec 15;99(12):3941-50. doi: 10.1016/j.bpj.2010.10.024.
The hierarchical packaging of DNA into chromatin within a eukaryotic nucleus plays a pivotal role in both the accessibility of genomic information and the dynamics of replication. Our work addresses the role of nanoscale physical and geometric properties in determining the structure of chromatin at the mesoscale level. We study the packaging of DNA in chromatin fibers by optimization of regular helical morphologies, considering the elasticity of the linker DNA as well as steric packing of the nucleosomes and linkers. Our model predicts a broad range of preferred helix structures for a fixed linker length of DNA; changing the linker length alters the predicted ensemble. Specifically, we find that the twist registry of the nucleosomes, as set by the internucleosome repeat length, determines the preferred angle between the nucleosomes and the fiber axis. For moderate to long linker lengths, we find a number of energetically comparable configurations with different nucleosome-nucleosome interaction patterns, indicating a potential role for kinetic trapping in chromatin fiber formation. Our results highlight the key role played by DNA elasticity and local geometry in regulating the hierarchical packaging of the genome.
真核细胞核内 DNA 以染色质的形式进行层级包装，这在基因组信息的可及性和复制动力学方面都起着关键作用。我们的工作旨在研究纳米级物理和几何特性在确定染色质的介观结构中的作用。我们通过优化规则螺旋形态来研究染色质纤维中的 DNA 包装，同时考虑连接 DNA 的弹性以及核小体和连接体的空间位阻。我们的模型预测了在固定 DNA 连接体长度下，广泛的螺旋结构偏好；改变连接体长度会改变预测的整体结构。具体来说，我们发现核小体的扭转登记（由核小体重复长度决定）决定了核小体与纤维轴之间的优选角度。对于中等至长的连接体长度，我们发现了许多能量相当的构型，具有不同的核小体-核小体相互作用模式，这表明动力学捕获在染色质纤维形成中可能发挥作用。我们的研究结果强调了 DNA 弹性和局部几何形状在调节基因组的层级包装中起着关键作用。
