Developmental acquisition of DNase I sensitivity of the phosphoenolpyruvate carboxykinase (GTP) gene in rat liver.

The sensitivity to DNase I digestion of the gene encoding rat phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) was assessed during development and prior to the onset of expression. This gene is resistant to DNase I digestion in nuclei isolated from livers of 19-day rat fetuses. Gradual acquisition of sensitivity of the phosphoenolpyruvate carboxykinase gene, which starts later than the 19th day of gestation and is completed by the 21st day, occurs before initiation of gene expression. As transcription of the phosphoenolpyruvate carboxykinase gene is not detected until birth, the events observed may represent a shift from a dormant to an active gene. Injection of N6,O2-dibutyryladenosine 3',5'-cyclic monophosphate into fetuses on the 19th day of gestation induces gene expression and sensitivity to DNase I digestion within 3 hr of treatment. While this short treatment does not affect the methylation pattern of the gene, longer treatment of fetuses (2 days) with dibutyryl-cAMP results in premature hypomethylation of the gene. A hierarchy of modifications of the phosphoenolpyruvate carboxykinase gene during development is discussed.