What is hemimethylated DNA?

At first, it took me a moment to wrap my  head around the concept of hemimethylation because I always seemed to get it mixed up with parental imprinting, which relies on parent-specific DNA methylation.

DNA-hemimethylation is when only one of two (complementary) strands is methylated. A hemi-methylated site is a single CpG that is methylated on one strand, but not on the other. This is not the same thing as allele-specific methylation, which is common in imprinting. In hemi-methylation, we’re talking about 2 strands from the same parent. Hemimethylation is important because it directly identifies de novo methylation events, allowing you to differentiation between de novo vs. maintenance factors. Because DNA methylation is faithfully propagated during DNA replication (by DNMT1), any hemimethylated sites must have arisen during the last replication round, either because: 1) failure to faithfully propagate a parental methylation signal; or, 2) a de novo methylation event. You can differentiate between the two if you know the methylation status of the parent: if the parent strand was entirely methylated, then hemimethylation indicates failure of maintenance. Vice versa, if the parent straned was unmethylated, hemimethylation indicates de novo methylation.