DNA Methylation and Expression of the Rat Pepsinogen Gene in Embryonic, Adult, and Neoplastic Tissues

The relationship between methylation and expression of rat pepsinogen 1 (Pgl) genes was investigated in various tissues. On Northern blotting with a Pgl complementary DNA probe, Pgl mRNA was detected only in the glandular stomach of normal rats. Methylation analysis with Msp1/HpaII and Hha1 revealed tissue specific methylation patterns of Pgl genes with less methylated in the stomach than in other normal tissues not expressing the genes. During stomach development, there was a progressive increase in the Pgl mRNA level that almost coincided with change in the mucosal pepsinogen level and progressive demethylation after the onset of transcription. Thus, there was an inverse correlation between methylation and expression of Pgl genes, suggesting a role of DNA methylation in Pgl gene regulation during normal differentiation, although not its primary role in gene activation. There was no detectable Pgl mRNA in either primary or transplanted stomach cancers induced by W-methyl-AT -nitro-7V-nitrosoguanidine. The methylation patterns of Pgl genes were different from those of normal tissues that expressed the gene and of those that did not and no simple correlation was observed between methylation and expression of Pgl genes. This result is consistent with a previous finding that DNA methylation is deranged in tumor cells.