Inhibition of DNA methylation by 5-azacytidine.
The nucleoside analog z5C induced marked changes in the differentiated state of mouse embryo cells and inhibited the methylation of newly synthesized DNA. Other analogs of cytidine containing modifications in the 5 position (5-aza-2'-deoxycytidine, 5-fluoro-2'-deoxycytidine, and pseudoisocytidine) also induced the formation of striated muscle cells in treated cultures and inhibited DNA methylation. Together the data suggests a causative role for the methylation of specific cytosine residues in the control of gene expression. Hemimethylated duplex DNA was extracted from cultures treated with z5C and was an efficient acceptor of methyl groups from S-adenosyl-methionine in the presence of a mouse spleen methyltransferase. The ability of this hemimethylated DNA to accept methyl groups was markedly impaired if it was pretreated with several different ultimate chemical carcinogens.
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors*; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D051379:Mice; D008809:Mice, Inbred C3H
D004247:DNA; D008780:Methyltransferases; D004248:DNA (Cytosine-5-)-Methyltransferases; D001374:Azacitidine