title: Direct evidence for sequence-dependent attraction between double-stranded DNA controlled by methylation.
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.
authors.affiliation: Department of Physics and the Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Jejoong
authors.initials: J
authors.lastname: Yoo
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea.|Center for Soft and Living Matter, Institute for Basic Science, Ulsan, Korea.
authors.forename: Hajin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Physics and the Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Aleksei
authors.initials: A
authors.lastname: Aksimentiev
authors.affiliation: Department of Physics and the Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.|Howard Hughes Medical Institute, Baltimore, Maryland 21205, USA.|Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, USA.|Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21205, USA.|Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Taekjip
authors.identifier: http://orcid.org/0000-0003-2195-6258
authors.initials: T
authors.lastname: Ha
mesh_terms: D020856:AT Rich Sequence; D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation; D020862:GC Rich Sequence; D056004:Molecular Dynamics Simulation; D012689:Sequence Homology, Nucleic Acid; D013096:Spermine / Q000378:metabolism
chemical_list: D013096:Spermine; D003596:Cytosine; D004247:DNA