5‑Methylation of Cytosine in CG:CG Base-Pair Steps: A Physicochemical Mechanism for the Epigenetic Control of DNA Nanomechanics

• Published in: The journal of physical chemistry. B Vol. 117; no. 51; pp. 16436 - 16442
• Main Authors: Yusufaly, Tahir I, Li, Yun, Olson, Wilma K
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.12.2013
• Subjects: Base Pairing; Chemical Phenomena; Crystal structure; Cytosine - chemistry; Cytosine - metabolism; Density functional theory; Deoxyribonucleic acid; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA Methylation; Epigenesis, Genetic; Models, Molecular; Modulation; Potential energy; Quantum Theory; Softening; Stacking
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp409887t

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.