The mechanical properties of a given DNA sequence dictate its nucleosome positioning propensity, and therefore may play an important role in gene regulation.  In particular, the nucleosome affinity of DNA sequences is higher in sequences that have dinucleotide repeated every 10 bp.  Likewise, CpG methylation of DNA is an epigenetic modification associated with the inactivation of transcription and the formation of a repressive chromatin structure. Understanding the changes in the structure of nucleosomes with various dinucleotide and upon CpG methylation and is necessary in providing insight of the mechanisms of gene repression. The  Density Functional Theory-Symmetry Adapted Perturbation Theory (DFT-SAPT) methods was utilized to systematically study the stacking effects of DNA fibers (18 bps length) as a function of both twist and rise (which is related to its bending propensity). The DFT-SAPT method provides insight into the p-stacking and hydrogen-bonded interactions of DNA structures on the basis of electrostatic and dispersion contributions. Our  findings suggest that changes in the physical properties of nucleosomes induced by methylation may contribute directly to the formation of a compacted chromatin structure.

Understanding the effects of DNA methylation on nucleosome stability from noncovalent interactions

245th National Meeting (2013)

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