Ozer Gungor, Collepardo-Guevara Rosana, Schlick Tamar
Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003,USA.
J Phys Condens Matter. 2015 Feb 18;27(6):064113. doi: 10.1088/0953-8984/27/6/064113. Epub 2015 Jan 7.
The chromatin fiber undergoes significant structural changes during the cell's life cycle to modulate DNA accessibility. Detailed mechanisms of such structural transformations of chromatin fibers as affected by various internal and external conditions such as the ionic conditions of the medium, the linker DNA length, and the presence of linker histones, constitute an open challenge. Here we utilize Monte Carlo (MC) simulations of a coarse grained model of chromatin with nonuniform linker DNA lengths as found in vivo to help explain some aspects of this challenge. We investigate the unfolding mechanisms of chromatin fibers with alternating linker lengths of 26-62 bp and 44-79 bp using a series of end-to-end stretching trajectories with and without linker histones and compare results to uniform-linker-length fibers. We find that linker histones increase overall resistance of nonuniform fibers and lead to fiber unfolding with superbeads-on-a-string cluster transitions. Chromatin fibers with nonuniform linker DNA lengths display a more complex, multi-step yet smoother process of unfolding compared to their uniform counterparts, likely due to the existence of a more continuous range of nucleosome-nucleosome interactions. This finding echoes the theme that some heterogeneity in fiber component is biologically advantageous.
染色质纤维在细胞生命周期中会经历显著的结构变化，以调节DNA的可及性。染色质纤维的这种结构转变受各种内部和外部条件（如介质的离子条件、连接DNA长度和连接组蛋白的存在）影响的详细机制，构成了一个开放性挑战。在此，我们利用蒙特卡罗（MC）模拟体内发现的具有非均匀连接DNA长度的染色质粗粒度模型，以帮助解释这一挑战的某些方面。我们使用一系列有无连接组蛋白的端到端拉伸轨迹，研究了连接长度交替为26 - 62 bp和44 - 79 bp的染色质纤维的展开机制，并将结果与连接长度均匀的纤维进行比较。我们发现连接组蛋白增加了非均匀纤维的整体抗性，并导致纤维通过“串上超级珠子”簇转变而展开。与连接长度均匀的染色质纤维相比，具有非均匀连接DNA长度的染色质纤维显示出更复杂、多步骤但更平滑的展开过程，这可能是由于存在更连续的核小体 - 核小体相互作用范围。这一发现呼应了纤维成分中的一些异质性在生物学上具有优势这一主题。
