Role of DNA 5-methylcytosine transferase in cell transformation by fos

The Fos and Jun oncoproteins form dimeric complexes that stimulate transcri ption of genes containing activator protein-1 regulatory elements. We found , by representational difference analysis, that expression of DNA 5-methylc ytosine transferase (dnmt1) in fos-transformed cells is three times the exp ression in normal fibroblasts and that fos-transformed cells contain about 20 percent more 5-methylcytosine than normal fibroblasts. Transfection of t he gene encoding Dnmt1 induced morphological transformation, whereas inhibi tion of dnmt1 expression or activity resulted in reversion of fos transform ation. Inhibition of histone deacetylase, which associates with methylated DNA, also caused reversion. These results suggest that fos may transform ce lls through alterations in DNA methylation and in histone deacetylation.