hemimethylation

Hemimethylation is a DNA state in which methyl groups are present on cytosines of only one strand of a double-stranded molecule. It most often arises at CpG dinucleotides in vertebrates when replication creates a hemi-methylated duplex: the parental strand retains methylation while the nascent strand is unmethylated.

In bacteria, methylation frequently occurs on adenine in GATC sequences (Dam methylation). After replication, GATC sites are hemimethylated until a maintenance methyltransferase acts. Hemimethylated DNA is recognized by SeqA and participates in the regulation of origin firing and in strand discrimination during mismatch repair, helping to distinguish the parental strand from the newly synthesized strand.

In eukaryotes, cytosine methylation at CpG sites is maintained by DNMT1 and cofactors such as UHRF1. After replication, DNMT1 is guided to hemi-methylated sites to copy methylation to the daughter strand, restoring symmetric methylation patterns used in gene regulation and chromatin organization. Hemimethylation thus serves as a transient mark signaling the restoration of the methylation pattern and can influence transcriptional activity and epigenetic inheritance.

Duration and significance: The hemi-methylated state is typically short-lived in actively dividing cells due to rapid maintenance methylation, but its presence can affect DNA-protein interactions, replication fidelity, and the recruitment of repair or chromatin-modifying complexes. Studying hemimethylation helps illuminate mechanisms of epigenetic inheritance and genome maintenance.