Differences in methylation patterns of the alpha-fetoprotein and albumin genes in hepatic and non hepatic developing...

By use of different restriction enzymes sensitive to internal cytosine methylation (HpaII, AvaI, HhaI) we have analysed the methylation patterns of albumin and AFP genes in tissues and cell lines with high (liver, yolk sac, hepatoma cell lines), low (fetal and neonatal kidney) or undetectable (spleen, JF1 fibroblasts) expression of either gene. We show that expression of the AFP gene is associated to the demethylation of a whole region or domain extending from -4 to +3 Kb. Moreover, demethylation of a site located at the upstream limit of this domain appears to be correlated with the commitment of the cell type to synthesize AFP. As concerns the albumin gene, we show that the domain in which demethylation is correlated with active gene transcription in hepatoma cell lines has different borders than in tissue. This difference might be related to the different amounts of mRNA synthesized or to an alteration in gene regulation in tumor cells. Finally, we show that low expression of albumin and AFP genes in fetal and neonatal kidney is not correlated with domain demethylation, suggesting that the regulatory mechanisms of expression of these genes are different in kidney as compared with liver.