Epigenetic Drugs: DNA Demethylating Agents

DNA methylation plays a critical role in the control of gene expression regulation. Aberrant DNA methylation of promoter-associated cytosine– guanine islands, and its associated aberrant epigenetic gene silencing, is considered a phenomenon functionally equivalent to physical genetic inactivation via mutations or deletions, and therefore it has a major role in oncogenesis. Histone acetylation leads to an open chromosome configuration and consequently to gene transcription and cell differentiation. Several enzymatic activities control this process of histone acetylation/deacytelation. The hypomethylating properties of cytosine derivatives were first noted by P. A. Jones and S. M. Taylor. In that study, cytidine analogs containing a modification at the 5 position induced myocyte differentiation in mouse embryo cells after a 24-hour incubation period. Several investigators have set out to study the hypomethylating effects of these compounds in vivo. Both global and the gene-specific hypomethylation have been evaluated in several studies.