Cytosine methylation alters DNA mechanical properties

DNA methylation plays an essential role in tran-scriptional control of organismal development in epigenetics, from turning off a specific gene to inactivation of entire chromosomes. While the bio-logical 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 methyla-tion 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 simula-tions 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 ex-pression not only through mechanisms already known but also through changing mechanical properties of DNA