School of Biological Sciences, Nanyang Technological University, Singapore.
Biophys J. 2010 Sep 22;99(6):1896-905. doi: 10.1016/j.bpj.2010.07.017.
The physical mechanism of the folding and unfolding of chromatin is fundamentally related to transcription but is incompletely characterized and not fully understood. We experimentally and theoretically studied chromatin compaction by investigating the salt-mediated folding of an array made of 12 positioning nucleosomes with 177 bp repeat length. Sedimentation velocity measurements were performed to monitor the folding provoked by addition of cations Na(+), K(+), Mg(2+), Ca(2+), spermidine(3+), Co(NH(3))(6)(3+), and spermine(4+). We found typical polyelectrolyte behavior, with the critical concentration of cation needed to bring about maximal folding covering a range of almost five orders of magnitude (from 2 μM for spermine(4+) to 100 mM for Na(+)). A coarse-grained model of the nucleosome array based on a continuum dielectric description and including the explicit presence of mobile ions and charged flexible histone tails was used in computer simulations to investigate the cation-mediated compaction. The results of the simulations with explicit ions are in general agreement with the experimental data, whereas simple Debye-Hückel models are intrinsically incapable of describing chromatin array folding by multivalent cations. We conclude that the theoretical description of the salt-induced chromatin folding must incorporate explicit mobile ions that include ion correlation and ion competition effects.
染色质的折叠和展开的物理机制从根本上与转录有关，但尚未完全阐明，人们对其了解也不充分。我们通过研究由 12 个定位核小体组成的阵列在盐介导下的折叠，从实验和理论两方面研究了染色质的紧缩。沉降速度测量用于监测阳离子 Na(+)、K(+)、Mg(2+)、Ca(2+)、亚精胺(3+)、Co(NH(3))(6)(3+)和精胺(4+)添加引起的折叠。我们发现了典型的聚电解质行为，使折叠达到最大所需的阳离子临界浓度范围跨越了近五个数量级（从精胺(4+)的 2 μM 到 Na(+)的 100 mM）。我们基于连续介电描述并包括可移动离子和带电荷的柔性组蛋白尾巴的核小体阵列粗粒模型用于计算机模拟，以研究阳离子介导的紧缩。具有显式离子的模拟结果通常与实验数据一致，而简单的 Debye-Hückel 模型本质上无法描述多价阳离子引起的染色质阵列折叠。我们得出结论，盐诱导的染色质折叠的理论描述必须包括包括离子相关和离子竞争效应的显式移动离子。
