Characterisation of developmentally regulated chromatin structure in the coding region of the proto-oncogene, c-fos, in the male laboratory mouse.

In mouse, tissue-specific developmental de novo methylation of the proto-oncogene c-fos, which is abundantly expressed during embryonic stages, occurs perinatally (between the day of birth to 20 dpp) and is maintained in the adult. In liver, where c-fos is only active up to the day of birth, the gene has more sites methylated than in brain, where it is expressed until about day 5 post-partum. We have studied chromatin organisation of c-fos and compared thisto DNA methylation in the fetal and adult brain and liver. Purified nuclei of these tissues from fetus as well as adult were digested with the restriction enzyme Mspl. DNA was extracted from the Mspl digested chromatin and probed with two DNA segments covering the major part of the body of the gene (from distal part of second exon to major part of fourth exon). Southern hybridisation studies revealed that in the fetus, in both liver and brain, the chromatin in the coding region was sensitive to Mspl digestion and the extent of sensitivity was nearly the same between the two. In the adult tissues, however, chromatin from brain was almost as sensitive as in the fetus, but in the liver it was highly resistant to Mspl. We suggest that a shift from the undermethylated state in the fetus to the heavy methylated state in the adult causes a corresponding change in the organisation of chromatin of c-fos in the coding region. Furthermore, the difference in the tissue-specificity in the methylation induced chromatin compaction could be due to differences in the transcription levels of c-fos and de novo methylation during early neonatal development.