5-Methylation of cytosine in CG:CG base-pair steps: a physicochemical mechanism for the epigenetic control of DNA nanomechanics

J Phys Chem B. 2013 Dec 27;117(51):16436-42. doi: 10.1021/jp409887t. Epub 2013 Dec 16.

Abstract

van der Waals density functional theory is integrated with analysis of a non-redundant set of protein-DNA crystal structures from the Nucleic Acid Database to study the stacking energetics of CG:CG base-pair steps, specifically the role of cytosine 5-methylation. Principal component analysis of the steps reveals the dominant collective motions to correspond to a tensile "opening" mode and two shear "sliding" and "tearing" modes in the orthogonal plane. The stacking interactions of the methyl groups globally inhibit CG:CG step overtwisting while simultaneously softening the modes locally via potential energy modulations that create metastable states. Additionally, the indirect effects of the methyl groups on possible base-pair steps neighboring CG:CG are observed to be of comparable importance to their direct effects on CG:CG. The results have implications for the epigenetic control of DNA mechanics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing*
  • Chemical Phenomena*
  • Cytosine / chemistry*
  • Cytosine / metabolism
  • DNA / chemistry*
  • DNA / genetics*
  • DNA / metabolism
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Models, Molecular
  • Quantum Theory

Substances

  • Cytosine
  • DNA