CpG methylation can regulate gene expression by altering the specific binding of protein and DNA. In order to understand how a single 5mC regulates protein-DNA interactions, we have compared the structures and dynamics of CEBP/βprotein-DNA complexes before and after methylation, and the results indicate that even a single 5mC can regulate protein-DNA recognition by steric-hindrance effect of methyl group and changing the hydrogen bond interactions. The interactions between the methyl group, mCpG motif, and the conserved residue arginine make the protein read out the variation of local environment, which further enhances the specific recognition and affects the base pair stacking. The stacking interactions can propagate along the backbone of DNA and lead to long-range allosteric effects, including obvious conformational variations for DNA base pairs.
Keywords: CREBP/β protein; Hydrogen bond; Methylation; Molecular modeling; Protein–DNA interaction.