De novo methylation of the proto-oncogene, c-fos, during development occurs step-wise and directionally in the laboratory mouse.
We have analyzed the ontogenic initiation and maintenance of methylation of certain Hpall (m), Hhal (H), Hincll (Hc), and Sall (SI)-specific CpG sites in the coding region of the proto-oncogene, c-fos, through testicular cells, sperm, and fetal, neonatal, and adult somatic tissues. The results show that 1) sperm-derived methylated sites get demethylated in early development. However, unlike other studied genes, they remain so at least up to day 13.5 post coitum (pc); 2) de novo methylation proceeds unidirectionally in a step-wise, site-specific manner between m5-m3 sites; 3) the mature, tissue-specific, adult methylation pattern is established between day 0 and day 20 of neonatal development; 4) the Hc and SI sites (CGTCGAC), occurring at an interval of one nucleotide, are only partially methylated in all the tissues; and 5) m3 and H1 sites, which occur close to an Sp1 motif, escape methylation in most of the tissues. The present study on the embryonic gene, c-fos, thus provides a novel pattern of de novo methylation in development. Also, it suggests that close proximity of CpGs may prevent methylation.
Chandrasekhar
K
K
Department of Zoology, Banaras Hindu University, Varanasi, India.
Raman
R
R
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002874:Chromosome Mapping; D018899:CpG Islands; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000378:metabolism; D016762:Genes, fos; D007668:Kidney / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism; D013154:Spleen / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013737:Testis / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D014018:Tissue Distribution