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This mechanism provides numerous possibilities for the precise regulation of the methyltransferases via controlling the binding and release of the autoinhibitory domains by protein partners, chromatin interactions, non-coding RNAs, or posttranslational modifications of the DNMTs. In this chapter, we summarize key enzymatic properties of DNMTs, viz. their specificity and processivity, and afterwards focus on the regulation of their activity and targeting via allosteric processes, protein interactions, and posttranslational modifications.I