Cytosine can undergo modifications, forming 5-methylcytosine (5-mC) and its oxidized products 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Despite their importance as epigenetic markers and as central players in cellular processes, it is not well understood how these modifications influence physical properties of DNA and chromatin. Here we report a comprehensive survey of the effect of cytosine modifications on DNA flexibility. We find that even a single copy of 5-fC increases DNA flexibility markedly. 5-mC reduces and 5-hmC enhances flexibility, and 5-caC does not have a measurable effect. Molecular dynamics simulations show that these modifications promote or dampen structural fluctuations, likely through competing effects of base polarity and steric hindrance, without changing the average structure. The increase in DNA flexibility increases the mechanical stability of the nucleosome and vice versa, suggesting a gene regulation mechanism where cytosine modifications change the accessibility of nucleosomal DNA through their effects on DNA flexibility.

中文翻译：

---

胞嘧啶修饰对DNA柔韧性和核小体机械稳定性的影响。

胞嘧啶可以进行修饰，形成5-甲基胞嘧啶（5-mC）及其氧化产物5-羟甲基胞嘧啶（5-hmC），5-甲酰基胞嘧啶（5-fC）和5-羧基胞嘧啶（5-caC）。尽管它们作为表观遗传标记和细胞过程中的核心角色很重要，但人们对这些修饰如何影响DNA和染色质的物理特性尚无甚了解。在这里，我们报告了胞嘧啶修饰对DNA柔韧性的影响的全面调查。我们发现，即使单个拷贝的5-fC也会显着提高DNA的柔韧性。5-mC降低而5-hmC增强灵活性，而5-caC则没有可测量的效果。分子动力学模拟表明，这些修饰可能通过碱基极性和位阻的竞争效应来促进或抑制结构波动，而不会改变平均结构。