Lehrstuhl für Angewandte Physik and Center for Nanoscience (CeNS), Ludwig-Maximilians-Universität, Munich, Munich, Germany.
Nucleic Acids Res. 2011 Nov 1;39(20):8740-51. doi: 10.1093/nar/gkr578. Epub 2011 Jul 20.
DNA methylation plays an essential role in transcriptional control of organismal development in epigenetics, from turning off a specific gene to inactivation of entire chromosomes. While the biological function of DNA methylation is becoming increasingly clear, the mechanism of methylation-induced gene regulation is still poorly understood. Through single-molecule force experiments and simulation we investigated the effects of methylation on strand separation of DNA, a crucial step in gene expression. Molecular force assay and single-molecule force spectroscopy revealed a strong methylation dependence of strand separation. Methylation is observed to either inhibit or facilitate strand separation, depending on methylation level and sequence context. Molecular dynamics simulations provided a detailed view of methylation effects on strand separation, suggesting the underlying physical mechanism. According to our study, methylation in epigenetics may regulate gene expression not only through mechanisms already known but also through changing mechanical properties of DNA.
DNA 甲基化在表观遗传学中对生物体发育的转录控制中起着至关重要的作用，从关闭特定基因到整个染色体失活。虽然 DNA 甲基化的生物学功能越来越清楚，但甲基化诱导基因调控的机制仍知之甚少。通过单分子力实验和模拟，我们研究了甲基化对 DNA 链分离的影响，这是基因表达的关键步骤。分子力测定和单分子力光谱揭示了甲基化对链分离的强烈依赖性。观察到甲基化抑制或促进链分离，具体取决于甲基化水平和序列背景。分子动力学模拟提供了关于甲基化对链分离影响的详细视图，表明了潜在的物理机制。根据我们的研究，表观遗传学中的甲基化可能不仅通过已知的机制，还通过改变 DNA 的力学性质来调节基因表达。
