Chromosome-21-dosage effect on inducibility of anti-viral gene(s)

Abstract

UNLIKE the bacterial situation little is known about gene regulation in mammalian cells. Inducible systems are being used to study regulatory gene functions in normal and abnormal mammalian cells^1–3, and have shown for example, that inhibitors of macromolecular synthesis enhance rather than inhibit the expression of an inducible enzyme. Actinomycin D enhances the induction of tyrosine aminotransferase (TAT) by steroid hormones in hepatoma cells⁴. Commonly referred to as superinduction, this effect has led to the hypothesis that a regulatory gene(s) modulates the expression of the structural TAT gene⁴. Of course, alternative explanations have been offered for the superinducing effect of actinomycin D (refs 5 and 6). Similarly, the induction of interferon by viruses and poly(I)·poly(C) and the induction of the anti-viral state (AVS) by interferon have been used to probe regulatory mechanisms in normal mammalian cells^7–13. It has been demonstrated that with judicious use of metabolic inhibitors the amount of interferon and the level of AVS induced can be enhanced 100–1,000 times and 10–100 times respectively, over that obtained in cultures exposed to inducer alone. This suggested that one or more regulatory gene(s) modulate the expression of the structural gene for interferon and AVS^7–19 I have used a new approach to assess the presence of a regulatory gene function which modulates the expression of the structural gene for AYS. 1 found evidence to suggest that the regulation of ithe anti-viral genes in human cells is controlled by regulatory gene element(s) located on a separate chromosome.