Molecular Modeling and Simulation (MMS) Group , National Institutes for Quantum and Radiological Science and Technology (QST) , 8-1-7, Umemidai , Kizugawa , Kyoto 619-0215 , Japan.
J Phys Chem B. 2018 Oct 25;122(42):9625-9634. doi: 10.1021/acs.jpcb.8b05067. Epub 2018 Oct 10.
The dimethylation of Arg at the 42nd position (R42me2) of H3 histone, a post-translational modification (PTM) in nucleosomes close to the DNA entry/exit region, showed controversial gene regulations. To address this discrepancy, we performed comprehensive all-atom replica-exchange molecular dynamics simulations with and without a single PTM, either symmetric (R42me2s) or asymmetric (R42me2a) dimethylation. Together with a kinetics analysis, our simulations showed that DNA at the entry/exit region in the R42me2a nucleosome adopts a relatively more open conformation than that in the unmodified nucleosome, whereas R42me2s exhibits significantly weaker or even negligible effects on DNA dynamics and structures, which may provide clues of the discrepancy of gene regulation by R42me2. Our approach will be useful to study the mechanism of nucleosome dynamical change induced by a subtle modification.
H3 组蛋白第 42 位精氨酸的二甲基化（R42me2）是核小体中靠近 DNA 进入/退出区域的一种翻译后修饰（PTM），它显示出了有争议的基因调控作用。为了解决这一分歧，我们进行了全面的全原子 replica-exchange 分子动力学模拟，分别模拟了带有和不带有单个 PTM 的情况，即对称（R42me2s）或不对称（R42me2a）二甲基化。结合动力学分析，我们的模拟表明，在 R42me2a 核小体中，DNA 在进入/退出区域的构象比在未修饰核小体中更开放，而 R42me2s 对 DNA 动力学和结构的影响显著较弱，甚至可以忽略不计，这可能为 R42me2 对基因调控的差异提供线索。我们的方法将有助于研究由细微修饰引起的核小体动力学变化的机制。
