Methylation of Reiterated Sequences in Mammalian DNAs. Effects of the Tissue Type, Age, Malignancy and Hormonal Induction

The content of 5-methylcytosine in sequences of various repetition degree obtained from some mammalian (rat, mouse, cow) DNAs has been studied. The minimal 5-methylcytosine content - about 0.8 mol% - is characteristic of unique DNA sequences of all DNAs studied; the maximal 5-methylcytosine content, usually exceeding 2 mol%, is found in most highly repeated sequences. The 5-methylcytosine content in low repetitive (10--1000-fold) sequences, which are known to contain genes for rRNA, tRNA and histones, is markedly higher than in unique sequences. In total DNAs of vertebrates, as well as in mammalian DNA fractions, 5-methylcytosine occurs at almost the same frequency as does dinucleotide (5')-CG-(3'). This suggests that a greater part (if not all) of 5-methylcytosine in mammalian DNAs is a product of DNA methylases which recognize the (5')-CG-(3') DNA sequence. In cows the 5-methylcytosine content in reiterated DNA sequences decreases in thymus and heart with age and in lymphocytes on chronic lympholeukosis. The methylation degree of reiterated sequences increases in rat liver DNA after administration of hydrocortisone. On the contrary, in all cases the extent of methylation of unique sequences hardly ever changes, which seems to result from nearly complete methylation of cytosine residues in sequence (5')-CG-(3'). Specific changes observed in tissue on methylation of reiterated DNA sequences on aging, leukosis and hormone treatment support the idea that DNA methylation is associated with cellular differentiation or transformation and may be one of the possible mechanisms for regulation of transcription and replication in eukaryotes.