Methylation, acetylation and phosphorylation of the bases of DNA of young and old rats.

The possibility of methylation, acetylation and phosphorylation of the bases of DNA has been studied in vitro by incubating nuclei of the liver and cerebral hemisphere of young (18 wk) and old (120 wk) rats with radioactive donors, [3H]S approximately adenosyl methylmethionine, [3H]-acetyl approximately CoA and [32P]-gamma-ATP for methylation, acetylation and phosphorylation of the bases, respectively. Nuclei were also incubated with S approximately adenosyl homocysteine to inhibit methylation with sodium butyrate to stimulate acetylation and with alkaline phosphatase to remove phosphate groups incorporated into the bases. DNA was then extensively purified and incorporation of each type of label was estimated. The data show that both methylation and acetylation of DNA of old rats were significantly higher than those of young rats, and phosphorylation is lower in old rats. Such modifications may prevent base pairing between the two strands of DNA, alter its conformation and binding of trans-acting factors at specific sites, and thereby alter gene expression.