Hypomethylation of DNA during differentiation of friend erythroleukemia cells

Abstract

DNA from mammalian cells contains significant amounts of 5-methyl cytosine resulting from enzymatic transfer of methyl groups from s-adenosylmethionine to cytosine residues in the DNA polymer. The function of this modification of this modification is not known. DNA synthesized during chemically induced differentiation of Friend [mouse] erythroleukemia cells is hypomethylated, as measured by its ability to accept methyl groups transferred by homologous DNA methyltransferases in vitro. The extent of hypomethylation detected by this sensitive method is small, a decrease of < 1.6% in 5-methylcytosine content. Hypomethylated DNA can be isolated from Friend erythroleukemia cells grown in the presence of dimethyl sulfoxide, butyrate, hexamethylene-bis-acetamide, pentamethylene-bis-acetamide and ethionine. Hypomethylated DNA is found only under conditions where differentiation is actually induced. DNA isolated from cells of a dimethyl sulfoxide-resistant subclone grown in the presence of that agent is not hypomethylated, although DNA of these cells becomes hypomethylated after growth in the presence of inducers that can trigger their differentiation. The DNA of Friend erythroleukemia cells does not become hypomethylated when the cells are exposed to inducing agents in the presence of substances that inhibit differentiation. A close link between genome modification by methylation and differentiation of Friend erythroleukemia cells was suggested.