The dynamic impact of CpG methylation in DNA

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 d inucleotide reduces the amplitudes of motions of the phosphate-sugar backbo ne. These observations suggest a direct link between suppression of the amp litudes of localized, internal motions of the sugar-phosphate backbone of t he DNA and inhibition of restriction enzyme cleavage.