RAS INDUCES A GENERAL DNA DEMETHYLATION ACTIVITY IN MOUSE EMBRYONAL P19 CELLS

We demonstrate that expression of v-Ha-ras in mouse embryonal P19 cell s results in genome-wide demethylation. Analysis of the pattern of met hylation of specific genes reveals that different types of genes are d emethylated in the ras transfectants: skeletal muscle specific genes, a gene specifically expressed in the adrenal cortex (c21), ubiquitous genes, and exogenously introduced sequences. Transient transfection an d in vitro demethylation assays reveal that the ras transfectants expr ess high levels of a general DNA demethylation activity. This demonstr ates that the general DNA demethylation activity in mouse embryonal ce lls is controlled by an important cellular signal transducer and that DNA demethylase is a potential downstream effector of Ras.