Regulation of Interferon-β Gene: Structure and Function ofcis-Elements andtrans-Acting Factors

Abstract

Commonly viral infections induce expression of type I interferon (IFN) genes. The induction is primarily due to transcriptional activation of the genes. Soon after the isolation of the genes encoding IFN-alpha and IFN-beta, the IFN system became a subject of intensive study in the context of switching on or off the otherwise silent genes by extracellular stimulation signals. Hence, the IFN system serves as a typical model in studying the genetic events occurring in many cytokine systems. The IFN genes contain within their 5'-flanking region positive elements that function efficiently in cells induced by viruses and other stimuli such as double-stranded RNA. At least three transcription factors have been identified and molecularly cloned. Of these, two factors, designated interferon regulatory factors IRF-1 and IRF-2, are unique in their function; they interact with identical DNA sequence elements of IFN and IFN-inducible genes. Results of the functional studies on these factors suggest that transcription of the IFN and IFN-inducible genes is regulated by two similar trans-acting factors that apparently compete for the same cis-acting recognition sequences, but mediate opposite effects.