The striking finding from this rather simple study was evidence of a demethylation, as opposed to the prevention of methylation. A recent paper on altered expression of interleukin-2 (IL-2) expression T lymphocytes following activation also clearly implicates an active process of demethylation in a normal differentiated somatic cell. Bruniquel and Schwartz122 found that a region in a promoter of the IL-2 gene demethylates following activation in the absence of DNA replication and results in a profound increase in the production of IL-2. These two papers provide the initial evidence for an active, environmentally driven alteration in DNA methylation in postmitotic cells. Szyf and colleagues101,123 first proposed that DNA methylation is enzymatically reversible and that DNA methylation is dynamic in fully differentiated cells. This idea remains controversial. Active demethylation was nevertheless clearly demonstrated early in embryogenesis and the parental genome undergoes replication independent, active demethylation hours after fertilization, well before the initiation of replication. Demethylation at very early stages in development has been relatively accepted, but the possibility of postnatal demethylation, especially in fully differentiated somatic cells, has been hotly disputed.
