FUNCTIONAL ROLES OF DNA METHYLATION
Species, tissue, and age specificity
We happened to be among the first, who in a rather skeptical general attitude, asked the question, “What is the biological significance of DNA methylation?”. Therefore, we endeavored to find various illustrative and adequate biological models that could be used for getting evidence of the significance of this genome modification. We learned a long time ago that DNA methylation is species specific. In many invertebrates the methylation degree of the genome is very low; as we have already mentioned, 5mC amount in Drosophila DNA is so small that it could not be detected for a very long time, whereas in vertebrate DNAs it is always present in noticeable amounts (Vanyushin, Tkacheva, et al., 1970); in plant DNA this base cannot even be called a minor base because its content is quite comparable with cytosine content (Vanyushin & Belozersky, 1959).
We have established that along with species specificity there are also tissue and age specificities of DNA methylation in animals (Berdyshev et al., 1967; Vanyushin, Mazin, et al., 1973;Vanyushin, Nemirovsky, et al., 1973; Vanyushin, Tkacheva, et al., 1970).These findings allowed us first to declare that DNA methylation should be a mechanism of regulation of gene expression and cell differentiation (Vanyushin, Mazin, et al., 1973). We also found that DNA methylation in mitochondria and the nucleus of one and the same animal or plant cell is different (Vanyushin, Alexandrushkina, & Kirnos, 1988;Vanyushin & Kirnos, 1974). Thus, the subcellular (organelle) specificity of DNA methylation was discovered. These data have drawn an attention of many investigators and pushed ahead the intense study of DNA methylation worldwide. Significant reductions in the genomic 5mC content upon aging were observed in mouse tissues (Wilson, Smith, Mag, & Cutler, 1987). The 5mC levels in DNA of different tissues (eg, brain, liver, intestinal mucosa) were observed to correlate with the chronological age. Now the age-dependent changes in DNA methylation are quite obvious, and some investigators are inclined even to consider DNA methylation degree as a sort of biological clock that measures the chronological age and forecasts life span (Florath, Butterbach, Muller, Bewerunge-Hudler, & Brenner, 2014). Distortions in DNA methylation may lead to premature aging.