DNA methylation properties: consequences for pharmacology

Abstract

DNA methylation plays an important role in controlling the profile of gene expression of mammalian cells. The hypothesis presented in this article by Moshe Szyf is that DNA methylation patterns are determined by an interplay between the level of DNA methyltransferase and demethylase activities and site-specific signals. The expression of the DNA methyltransferase gene is regulated with the proliferative state of the cell and it is upregulated by cellular oncogenic pathways, resulting in hypermethylation and repression of tumour-suppressing loci. DNA methyltransferase inhibitors would inhibit the excessive activity of DNA methyltransferase in cancer cells and induce the original cellular programme of tumour suppression. They can also be used to turn on alternative programmes of gene expression. Specific DNA methyltransferase antagonists might provide us with therapeutic agents directed at a nodal point of regulation of genetic information.