Graduate School of Management of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
Int J Mol Sci. 2022 Jun 9;23(12):6467. doi: 10.3390/ijms23126467.
Cytosine methylation within the 5'-C-phosphate-G-3' sequence of nucleotides (called CpG methylation) is a well-known epigenetic modification of genomic DNA that plays an important role in gene expression and development. CpG methylation is likely to be altered in the CpG islands. CpG islands are rich in cytosine, forming a structure called the i-motif via cytosine-cytosine hydrogen bonding. However, little is known about the effect of CpG methylation on the i-motif. In this study, The CpG methylation-induced structural changes on the i-motif was examined by thermal stability, circular dichroism (CD) spectroscopy, and native-polyacrylamide gel electrophoresis (Native-PAGE) evaluation of five i-motif-forming DNAs from four cancer-related genes (, , , and ). This research shows that CpG methylation increased the transitional pH of several i-motif-forming DNAs and their thermal stability. When examining the effect of CpG methylation on the i-motif in the presence of opposite G4-forming DNAs, CpG methylation influenced the proportion of G4 and i-motif formation. This study showed that CpG methylation altered the stability and structure of the i-motif in CpG islands.
核苷酸 5'-C-磷酸-G-3'序列中的胞嘧啶甲基化（称为 CpG 甲基化）是基因组 DNA 中一种众所周知的表观遗传修饰，在基因表达和发育中发挥着重要作用。CpG 甲基化很可能在 CpG 岛上发生改变。CpG 岛富含胞嘧啶，通过胞嘧啶-胞嘧啶氢键形成一种称为 i -motif 的结构。然而，关于 CpG 甲基化对 i-motif 的影响知之甚少。在这项研究中，通过热稳定性、圆二色性（CD）光谱和来自四个癌症相关基因（、、、和）的五个 i-motif 形成 DNA 的天然聚丙烯酰胺凝胶电泳（Native-PAGE）评估，研究了 CpG 甲基化对 i-motif 的结构变化。这项研究表明，CpG 甲基化增加了几个 i-motif 形成 DNA 的过渡 pH 值及其热稳定性。当研究 CpG 甲基化对存在相反 G4 形成 DNA 时的 i-motif 的影响时，CpG 甲基化影响了 G4 和 i-motif 形成的比例。这项研究表明，CpG 甲基化改变了 CpG 岛中 i-motif 的稳定性和结构。
