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Nat Commun. 2016 Mar 22;7:11045. doi: 10.1038/ncomms11045.

Direct evidence for sequence-dependent attraction between double-stranded DNA controlled by methylation.

Yoo J1, Kim H2,3, Aksimentiev A1,4, Ha T1,5,6,7,8.

Author information

1
Department of Physics and the Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
2
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.
3
Center for Soft and Living Matter, Institute for Basic Science, Ulsan, Korea.
4
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
5
Howard Hughes Medical Institute, Baltimore, Maryland 21205, USA.
6
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, USA.
7
Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21205, USA.
8
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205, USA.

Abstract

Although proteins mediate highly ordered DNA organization in vivo, theoretical studies suggest that homologous DNA duplexes can preferentially associate with one another even in the absence of proteins. Here we combine molecular dynamics simulations with single-molecule fluorescence resonance energy transfer experiments to examine the interactions between duplex DNA in the presence of spermine, a biological polycation. We find that AT-rich DNA duplexes associate more strongly than GC-rich duplexes, regardless of the sequence homology. Methyl groups of thymine acts as a steric block, relocating spermine from major grooves to interhelical regions, thereby increasing DNA-DNA attraction. Indeed, methylation of cytosines makes attraction between GC-rich DNA as strong as that between AT-rich DNA. Recent genome-wide chromosome organization studies showed that remote contact frequencies are higher for AT-rich and methylated DNA, suggesting that direct DNA-DNA interactions that we report here may play a role in the chromosome organization and gene regulation.

PMID:
27001929
PMCID:
PMC4804163
DOI:
10.1038/ncomms11045
[Indexed for MEDLINE]
Free PMC Article

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