Differential response of the human 6–16 and 9–27 genes to α and γ interferons

Abstract

9-27 mRNA is expressed to a high level in response to both alpha and gamma interferons. In contrast, 6-16 mRNA is expressed well in response to alpha but very poorly in response to gamma interferon in human cells. The factors governing these different levels of expression were investigated. For both genes the major effect of both interferons is on transcription. A transcriptional bias in the 6-16 promoter/enhancer accounts in large part for the differential response of 6-16 to the two interferons. No single DNA element appears responsible; the smaller the 5' region analysed the lower the absolute activity and the smaller the differential response to alpha and gamma interferons observed. Both the 6-16 and 9-27 mRNAs are very stable and no effect of the interferons on stability was detected. Nor was any direct evidence obtained for preferential processing of the 9-27 mRNA. Nevertheless, differentials between the transcription and accumulation of mature mRNAs, particularly for 6-16 mRNA in response to gamma interferon, suggest that post-transcriptional control(s) must additionally operate. The 9-27 5' promoter/enhancer is much less active than that from 6-16 when placed 5' of a marker gene, despite the similar response of the two genes to alpha interferon.

Gene targeting in human somatic cells

“…Secondly, the interferon-induced genes with known immunoregulatory functions lie in the MHC locus on chromosome 6 and are induced by type I1 interferon in addition or in preference to being induced by type I interferon [25, 511. In contrast, 6-16 is preferentially induced by type I interferons [52] and is located on chromosome 1 [13, 531. Of the genes induced preferentially by type I interferon, only one (the Mx gene) has a known function but this is antiviral These considerations in no way discount the possibility that 6-1 6 is required for the antiproliferative or immunoregulatory effects of interferon, and experiments to test specific effects, such as the regulation of antigen presentation, may be revealing. In an initial examination, clone 2.1 was found to be unaffected, compared to HT1080 and clone 2.1', in its cell-surface expression of MHC class I molecules before or after treatment with interferon (Dallman M., Nuffield Department of Surgery, Oxford; personal communication).…”

IFITM1 plays an essential role in the antiproliferative action of interferon-γ

“…Transcription of IFITM1 is responsive to IFN-g, as well as IFN-a (Friedman et al, 1984;Kelly et al, 1985). The IFITM1 mRNA is stable, and no effect of IFN-g on mRNA stability was detected (Ackrill et al, 1991), indicating that IFN-g induces the de novo synthesis of IFITM1. An interferon-stimulated response element (ISRE) in the 5 0 flanking region of IFITM1 gene can confer both IFN-a and IFN-g inducibility to IFITM1 (Reid et al, 1989).…”

Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays

“…The other well characterized category of ISGs includes the signal transducer and activator of transcription (STAT) and IFN regulatory factor (IRF) families of transcription factors, which are involved in the regulation of both ISG and IFN gene expression (1,3,4). However, the biological functions for many ISGs, including 6-16, 9-27, and the ISG-54 gene family, remain unclear despite, in some cases, extensive investigation of the 5Ј regulatory regions of those genes (5)(6)(7).…”