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한빛사논문
한빛사논문
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University of Illinois, Urbana-Champaign, Johns Hopkins University, Howard Hughes Medical Institute
Nat. Commun., Published 24 February 2016, 7, Article number: 10813 | doi:10.1038/ncomms10813
Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability
Abstract
Thuy T.M. Ngo1, Jejoong Yoo2, Qing Dai3,4,5, Qiucen Zhang2, Chuan He3,4,5,6, Aleksei Aksimentiev1,2 & Taekjip Ha1,2,7,8,9,10
1 Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. 2Department of Physics and Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. 3Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, USA. 4Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, USA. 5 Institute for Biophysical Dynamic, The University of Chicago, Chicago, Illinois 60637, USA. 6Howard Hughes Medical Institute, Chicago, Illinois 60637, USA. 7Howard Hughes Medical Institute, Baltimore, Maryland 21205, USA. 8Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, USA. 9Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21205, USA. 10Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Correspondence and requests for materials should be addressed to T.H..
Correspondence and requests for materials should be addressed to T.H..
Abstract
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 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.
논문정보
- Research article
- 2016년 02월 (BRIC 등록일 2016-03-02)
- 국외 연구진
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