Regulation of carbamoyl phosphate synthetase-aspartate transcarbamoylase-dihydroorotase gene expression in growing and arrested cells.

We have studied expression of the carbamoyl-P synthetase-aspartate transcarbamoylase-dihydroorotase (CAD) gene in growing or confluent Syrian hamster cells, and also in cells arrested by depriving them of serum or restimulated by adding fresh serum. In contrast to other biosynthetic enzymes such as dihydrofolate reductase, the amount of the CAD enzyme decreased very little when growth was arrested, as judged by the small change in aspartate transcarbamoylase activity. However, the level of CAD mRNA was about 10-fold lower in arrested cells than in growing cells. The rate of transcription of CAD, measured by the nuclear run-off technique, decreased roughly in parallel with the decrease in the steady-state level of the mRNA, suggesting that control of transcription is probably an important element in the overall regulation of CAD gene expression. Expression of a different gene which lies near the 5' end of CAD changed in parallel with that of CAD, but expression of two other genes in the same region was insensitive to the growth state of the cells. Therefore, control of gene expression as a function of growth was specific rather than a reflection of more general changes in chromatin structure in the vicinity of CAD.