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Nat Commun. 2016 Feb 24;7:10813. doi: 10.1038/ncomms10813.

Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability.

Ngo TT1, Yoo J2, Dai Q3,4,5, Zhang Q2, He C3,4,5,6, Aksimentiev A1,2, Ha T1,2,7,8,9,10.

Author information

1
Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
2
Department of Physics and Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
3
Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, USA.
4
Department 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.
6
Howard Hughes Medical Institute, Chicago, Illinois 60637, USA.
7
Howard Hughes Medical Institute, Baltimore, Maryland 21205, USA.
8
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, USA.
9
Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21205, USA.
10
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205, USA.

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.

PMID:
26905257
PMCID:
PMC4770088
DOI:
10.1038/ncomms10813
[Indexed for MEDLINE]
Free PMC Article

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