The Dynamic Impact of CpG Methylation in DNA

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Abstract
Solid-state deuterium NMR is used to investigate perturbations of the local, internal dynamics in the EcoRI restriction binding site, -GAATTC- induced by cytidine methylation. Methylation of the cytidine base in this sequence is known to suppress hydrolysis by the EcoRI restriction enzyme. Previous solid-state deuterium NMR studies have detected large amplitude motions of the phosphate−sugar backbone at the AT−CG junction of the unmethylated DNA sequence. This study shows that methylation of the cytidine base in a CpG dinucleotide reduces the amplitudes of motions of the phosphate−sugar backbone. These observations suggest a direct link between suppression of the amplitudes of localized, internal motions of the sugar−phosphate backbone of the DNA and inhibition of restriction enzyme cleavage.