44 Positive and Negative Control of Human Interferon-β Gene Expression

Abstract

OVERVIEW Expression of the human interferon-β (IFN-β) gene is transiently induced by virus infection. The regulatory sequences required for this on/off switch are located within a 100-bp regulatory element located immediately upstream of the start site of transcription. This region contains at least three distinct virus-inducible elements and two negative regulatory elements. The mechanism of virus induction is thought to involve the inactivation or displacement of repressor proteins bound to the negative elements, and combinatorial interactions between virus-inducible factors that specifically bind to the three distinct positive regulatory elements. The gene is then turned off after induction by virus-inducible repressors that bind to the positive control elements. In this review, we summarize our current understanding of the organization of the IFN-β gene promoter and recent studies of transcriptional activators and repressors that bind to specific sites within the promoter. INTRODUCTION The IFN-β gene is highly inducible by virus or double-stranded RNA (for review, see DeMaeyer and DeMaeyer-Guignard 1988). Prior to virus induction, the level of IFN-β gene mRNA is too low to be detected, but within hours after infection, over 2000 transcripts per cell are produced. Virus induction is transient, however, since the level of IFN-β mRNA peaks 6–12 hours after induction, then decreases rapidly. This burst of mRNA synthesis leads to the transient production of IFN-β, a secreted protein that binds to a specific cell-surface receptor. The bound receptor triggers a signal transduction pathway leading to the activation of a large number of genes encoding antiviral proteins. Virus...