How M.Mspl and M.Hpall decide which base to methylate

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Abstract
The Hpall methylase (M.Hpall) recognizes the sequence CCGG and methylates the inner cytosine residue. The Mspl methylase (Mspl) recognizes the same sequence but methytates the outer cytosine residue. Both methylases have the usual architecture of 10 well-conserved motifs surrounding a variable region, responsible for sequence specific recognition, that is quite different in the two methyiases. We have constructed hybrids between these two methylases and studied their methylation properties. A hybrid containing the variabie region and C-terminal sequences from M.Mspl methylates the outer cytosine residue. A second hybrid identical to the first except that the variable region derives from the M.Hpall methylates the inner cytosine residue. Thus the choice of base to be methylated within the recognition sequence is determined by the variable region.