Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Hiroshima, Japan.
RIKEN Center for Biosystems Dynamics Research (BDR), Wako, Saitama, Japan.
Phys Rev E. 2021 Jan;103(1-1):012404. doi: 10.1103/PhysRevE.103.012404.
DNA methylation is associated with a number of biological phenomena, and plays crucial roles in epigenetic regulation of eukaryotic gene expression. It is also suggested that DNA methylation alters the mechanical properties of DNA molecules, which is likely to affect epigenetic regulation. However, it has not been systematically investigated how methylation changes the structural and dynamic features of DNA. In this research, to elucidate the effects of methylation on DNA mechanics, a fully atomic molecular dynamics simulation of double-stranded DNA with several methylation patterns was performed. Through the analysis of the relative positioning of the nucleotides (base-step variables), characteristic changes in terms of local flexibility were observed, which further affected the overall DNA geometry and stiffness. These findings may serve as a basis for a discussion on methylation-dependent DNA dynamics in physiological conditions.
DNA 甲基化与许多生物现象有关，在真核生物基因表达的表观遗传调控中起着关键作用。此外，DNA 甲基化还会改变 DNA 分子的力学性质，从而可能影响表观遗传调控。然而，甲基化如何改变 DNA 的结构和动态特征这一问题尚未得到系统研究。在这项研究中，为了阐明甲基化对 DNA 力学的影响，我们对几种甲基化模式的双链 DNA 进行了全原子分子动力学模拟。通过分析核苷酸的相对位置（碱基步变量），我们观察到了局部灵活性方面的特征变化，这些变化进一步影响了 DNA 的整体几何形状和刚性。这些发现可能为讨论生理条件下依赖于甲基化的 DNA 动力学提供基础。
