Age-dependent and tissue-specific changes of DNA methylation within and around the c-fos gene in mice

The degreee of DNA methylation in the c-fos gene and its vicinity in liver, brain and spleen of mice of different ages was examined using methylation-sensitive restriction endonucleases. The gene had an invariable unmethylated domain from 1.8 kb upstream of the cap site to the first intron. The domain was flanked on both sides with partially methylated areas, where tissue-specificity and age-dependent changes were observed. The tissue-specificity was found on the 14th day of gestation. Increases of methylation were observed during the late fetal and one month postnatal developmental periods in the three tissues. After that, the methylation states remained unchanged. One exception was seen in the exon 2 area in liver, were methylation continued to increase throughout life. This revealed the importance of the late fetal- and post-natal developmental periods in the establishment of tissue-specificity in DNA methylation profiles and further showed that some of the developmental changes could extend into the senescent phase.