Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: XVIII. Biomethylation and differentiation.

Many reports have appeared describing a direct relationship between hypomethylated states of genes and gene activity. Even after the introduction of viral genomes, these new genes appear to be controlled by specific DNA methylations. A variety of other studies have shown chromatin structural changes being implicated in the activities of certain gene loci. Modifications of chromatin domains may also be initiated or under the control of methylation reactions. Embryonic genes may be controlled by particular methylations by virtue of a differential (hyper-) sensitivity to concentrations of active methyl groups, on a variety of chromatin domains thereby explaining the variation in S-adenosyl-L-methionine synthesis required in developing liver tissue. Also our finding of the ability to manipulate experimentally the activity of the alpha-fetoprotein gene by methyl group availability indicates some methyl-sensitive mechanism is operating with respect to embryonic genes.