Ras induces a general DNA demethylation activity in mouse embryonal P19 cells.
We demonstrate that expression of v-Ha-ras in mouse embryonal P19 cells results in genome-wide demethylation. Analysis of the pattern of methylation of specific genes reveals that different types of genes are demethylated 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 and in vitro demethylation assays reveal that the ras transfectants express high levels of a general DNA demethylation activity. This demonstrates that the general DNA demethylation activity in mouse embryonal cells is controlled by an important cellular signal transducer and that DNA demethylase is a potential downstream effector of Ras.
Szyf
M
M
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Theberge
J
J
Bozovic
V
V
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D004247:DNA / Q000378:metabolism*; D015254:DNA Modification Methylases / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D011905:Genes, ras / Q000235:genetics; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011950:Receptors, Cholinergic / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D018243:Teratocarcinoma / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D011950:Receptors, Cholinergic; D011994:Recombinant Proteins; D004247:DNA; D013255:Steroid 21-Hydroxylase; D015254:DNA Modification Methylases; D008780:Methyltransferases