Direct evidence for sequence-dependent attraction between double-stranded DNA controlled by methylation
Jejoong Yoo, Hajin Kim, Aleksei Aksimentiev & Taekjip Ha
Affiliations Contributions Corresponding authors
Nature Communications 7, Article number: 11045 doi:10.1038/ncomms11045
Received 17 September 2015 Accepted 16 February 2016 Published 22 March 2016
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.
Subject terms: Biological sciences Biochemistry Biophysics Molecular biology
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