Kazuhiro Sogawa

Hypomethylation and expression of pepsinogen a genes in the fundic mucosa of human stomach

We have examined the correlation between the extents of methylation and expression of pepsinogen A genes in normal human tissues. Expression of pepsinogen A mRNA was detected only in the fundic mucosa of the stomach and both CCGG and GCGC sites in the genes region were less methylated in the fundic mucosa than in other non-expressing tissues. Thus, there was an inverse correlation between the extents of methylation and expression of pepsinogen A genes and the role of DNA methylation in the regulation of pepsinogen A genes expression during normal differentiation was suggested.

Close linkage of human chromosomal pepsinogen A genes

We have obtained a clone containing two pepsinogen A genes in a single insert by screening a recombinant cosmid library for human genomic DNA. Restriction endonuclease mappings of this cloned DNA showed that these two genes are very similar, but distinct in structure, and that they are closely linked to one another in the human chromosome DNA. The close arrangement of the genes with very similar structures could facilitate the homologous recombination or the unequal crossing-over which accounts for high frequency of haplotype variation in copy number of pepsinogen A genes as reported by Taggart et al.

Multiplicity of cytochrome P-450 and its gene structure

Cytochrome P-450 is widely distributed in nature from microorganisms to higher animals and plays an important role in the oxidative metabolism of a great variety of endogenous as well as exogenous lipophilic compounds (Sato & Omura, 1978; Lu & West, 1980). Recent studies involving immunological chemistry and protein chemistry have shown that multiple forms of cytochrome P-450 are present in rat liver microsomes and that their synthesis could be induced in different ways by the administration of various kinds of drugs (Sato & Omura, 1978; Lu & West, 1980). However, the molecular multiplicity and drug induction mechanism of cytochrome P-450 could best be understood by investigation at the gene (DNA) level using recombinant DNA technology.