Effect of DNA methylation in vitro on the expression of SV40 and VSPV

The biological function of eukaryotic DNA methylation is still an enigma. In the past two years, however, a growing number of publications has reported a correlation between the transciptional activity of eukaryotic and viral genes and their undermethylation (Desrosiers et al., 1979; Sutter and Doerfler, 1980; Compere and Palmiter, 1981). Without so far constituting a direct proof, these reports suggest an important role for eukaryotic DNA methylation in gene regulation and cell differentiation. Efforts should now be concentrated on establishing direct evidence for the implication of DNA methylation in gene regulation and on clarifying its mechanism. We purified a DNA methylase from rat liver, methylated double stranded (ds) DNA from SV40 and single stranded (ss) DNA from very small porcine virus, VSPV, (Tischer et al., 1981) in vitro, and compared the biological properties of the methylated viral DNAs with the corresponding unmethylated control DNAs. Whereas methylated and unmethylated SV40 DNA behaved identically after injection into permissive as well as into nonpermissive cells, significant differences became evident between methylated and unmethylated VSPV genomes. The effectivity of transfection with methylated VSPV DNA was only about 1% of the unmethylated control.