Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability

• Published in: Nature communications Vol. 7; no. 1; p. 10813
• Main Authors: Ngo, Thuy T. M., Yoo, Jejoong, Dai, Qing, Zhang, Qiucen, He, Chuan, Aksimentiev, Aleksei, Ha, Taekjip
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24-02-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 14/33; 5-Methylcytosine - metabolism; 631/45/147; 631/45/535; 631/45/612/100/1701; 631/57/2272; Biomechanical Phenomena; Cytosine - analogs & derivatives; Cytosine - metabolism; DNA - metabolism; DNA Methylation; Humanities and Social Sciences; Molecular Dynamics Simulation; multidisciplinary; Nucleosomes - metabolism; Oxidation-Reduction; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10813

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.
Cytosine modifications are important epigenetic markers yet their physical influence on DNA is not well understood. Here, Ngo
et al
. show that different alterations affect DNA flexibility, suggesting a mechanism where modifications change accessibility of nucleosome bound DNA.