A study of the mechanism of selenite-induced hypomethylated DNA and differentiation of Friend erythroleukemic cells

Sodium selenite is a good inducer of hemoglobin production inFriend erythroleukemic cells (FELC). At a concentration of 20µM 70-80% of the cells produce hemoglobin and the DNAis hypomethylated. What is the mechanism for sodium selenitealteration of the DNA methylation pattern? Experiments withmethionine adenosyltransferase (the enzyme that synthesizesadenosylmethionine) showed little effect of selenite on theactivity of this enzyme in vitro or in vivo. Therefore, FELCare able to synthesize S-adenosyhnethionine in the presenceof sodium selenite. When sodium selenite was added to an invitro assay for DNA methylase, the enzyme was non-competitivelyinhibited by 80% at 20 µM selenite with a K₁ of 6 µM.DNA methylase isolated from control and selenite-treated FELCwas purified through a DEAE-Sephacel column and no differencein activity was found. In the presence of selenite, DNA methylaseis very sensitive to selenite inhibition, but removal of theselenite restores activity. However, DNA synthesized by FELCgrown in the presence of selenite (no DNA methylase activity)was found to be hypomethylated. These results suggest that DNAmethylase activity is inhibited in FELC grown in the presenceof sodium selenite.