Yes, SacI-HF and SacI differ in their sensitivity to overlapping mammalian CpG methylation. SacI-HF™ is blocked by overlapping methylation on both strands and impaired if one strand is methylated. SacI cuts if one or both strands contain overlapping CpG methylation. Both enzymes cut EcoBI overlapping adenine methylation. For more specific information regarding methylation, follow the link to the Restriction Enzyme database REBASE.