DNA methylation is a reversible biological signal

The pattern of DNA methylation plays an important role in regulating differ ent genome functions. To test the hypothesis that DNA methylation is a reve rsible biochemical process, we purified a DNA demethylase from human cells that catalyzes the cleavage of a methyl residue from 5-methyl cytosine and its release as methanol. We show that-similar to DNA methyltransferase, DNA demethylase shows CpG dinucleotide specificity, can demethylate mdCpdG sit es in different sequence contexts, and demethylates both fully methylated a nd hemimethylated DNA. Thus, contrary to the commonly accepted model, DNA m ethylation is a reversible signal, similar to other physiological biochemic al modifications.