TY - JOUR
T1 - Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability
AU - Ngo, Thuy T.M.
AU - Yoo, Jejoong
AU - Dai, Qing
AU - Zhang, Qiucen
AU - He, Chuan
AU - Aksimentiev, Aleksei
AU - Ha, Taekjip
N1 - Funding Information:
This work was supported by the US National Institutes of Health (GM065367) and by the National Science Foundation Physics Frontier Center programme (PHY-1430124) to T.H., HG006827 to C.H. and K01HG006699 to Q.D. T.H. and C.H. are investigators with the Howard Hughes Medical Institute.
PY - 2016/2/24
Y1 - 2016/2/24
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms10813
DO - 10.1038/ncomms10813
M3 - Article
C2 - 26905257
AN - SCOPUS:84959432574
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 10813
ER -