[DNA methylation and interaction with glucocorticoid receptor complexes in the rat liver].

DNA from the livers of 20-day-old rat embryos contains 1.8 mol.% of 5-methylcytosine (m5C), i.e., it is methylated approximately 2-fold as compared with adult (m5C = 1.0 mol.%) and aged (20-month-old; m5C = 0.9 mol.%) animals. 90 min after intraperitoneal injection of adult adrenalectomized rats with hydrocortisone (5 mg per 100 g of body weight), the m5C content in liver DNA becomes 0.7 mol.%, i.e., it decreases by about 30% against control values. It was assumed that hydrocortisone induces enzymatic demethylation of m5C residues in rat liver DNA. A comparative study of competition between the DNA under study and DNA-cellulose for the binding to highly purified (approximately 2000-fold) glucocorticoid-receptor complexes (GRC) of rat liver revealed that the highly methylated rat embryo liver DNA bind the activated [3H]triamcinolone-receptor complexes with a lower (approximately 1.8-2 times) efficiency than do the DNA from the livers of adult and aged rats, including the hydrocortisone-induced ones. An inverse correlation was observed between the m5C level in rat liver DNA and the ability of the latter to bind GRC. After in vitro methylation of liver DNA of adult rats in the presence of S-adenosylmethionine by DNA-methylase from blood lymphocytes of suffering from chronic lympholeukosis cows, the GRC-receptor ability of these DNA was practically lost. Hence, GRC of rat liver can recognize sequences that are recognizeable by animal DNA-methylase. The observed modulations in the RNA-methylation upon ageing and those induced by hydrocortisone can control the effectiveness of glucocorticoid hormone action on gene expression in ontogenesis and at various inducible functional states of the organism.