The expression of liver-specific genes within rat embryonic hepatocytes is a discontinuous process

The onset of transcription and mRNA accumulation of two liver-specific genes, carbamoylphosphate synthase (CPS) and phosphoenolpyruvate carboxykinase (PEPCK) in individual embryonic rat hepatocytes was investigated with in situ hybridization. In vitro CPS and PEPCK mRNAs can be induced prematurely in monolayer cultures of embryonic rat hepatocytes by glucocorticosteroids and cyclic AMP, i.e. the hormones that also regulate the expression of these genes in vivo. Upon exposure to hormones the cultures showed an interhepatocyte heterogeneity in CPS and PEPCK mRNA content. The pattern of accumulation of nuclear CPS mRNA-precursors indicates that this heterogeneity is generated by intercellular differences in the timing of the onset of transcription. However, under induced steady-state conditions the heterogeneity in the hepatocyte population persisted. The degree of heterogeneity is inversely related to the half life of the gene product (i.e. higher for PEPCK than for CPS and higher for mRNAs than for the respective proteins) and to the concentrations of inducing hormones. Accordingly, the interhepatocyte heterogeneity was most pronounced for the nuclear CPS mRNA-precursor. In contrast, no intercellular differences in the rate of degradation of the mRNAs were seen. These observations reveal that although all hepatocytes can and do express the genes, transcription of a gene in a particular cell is a discontinuous process.