Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons.

Abstract

The gene encoding a 67-kDa cytoplasmic guanylate-binding protein (GBP) is transcriptionally induced in cells exposed to interferon of either type I (alpha interferon [IFN-a] or INF-,) or type II (IFN--y 20,30,31). A DNA-binding protein termed ISGF-3 is responsible for the IFN-x-dependent activation through the ISRE. This conclusion is based on a variety of evidence, including the parallel induction of ISGF-3 and transcription even in the absence of ongoing protein synthesis (19,20), and on in vitro transcriptional activation of an ISRE-containing promoter by ISGF-3 (13a). Other factors bind to the ISRE, but their role, if any, in IFN-regulated transcription is unknown (7,19,20,34,36 Given a clearly defined DNA site that is relevant for transcriptional induction by IFN--y, proteins must be found and defined that fulfill the requirements of transcriptional activators. Blanar et al. (2) have proposed that an IFN-yinducible ISRE-binding factor, which they termed IBP-1, mediates the response of the H2-Kb gene to IFN-y. On the basis of its apparent molecular weight, ISRE-binding characteristics, and IFN--y inducibility, IBP-1 is probably identical to the previously described ISGF-2 (also called IRF-1) (25,28). Is ISGF-2 (IRF-1, IBP-1) the factor responsible for the response of ISRE-containing genes to IFN--y? In this report, we describe the cloning and characterization of the promoter of the guanylate-binding protein (GBP) gene, which is inducible by both IFN types (3,8,21

Co-occupancy of the interferon regulatory element of the class II transactivator (CIITA) Type IV promoter by interferon regulatory factors 1 and 2

“…The same nuclear extracts (40 mg) used for the EMSA shown in (b) and (c) were analysed for IRF-2 protein by Western blotting, as described in Materials and methods function in Hs766T (Figures 6 and 7) reduces but does not abolish IFN-g response of GBP gene ( Figure 8 and Table 1). The partial GBP induction by IFN-g could be attributable to activated STAT1, which binds to the GAS element overlapping with the IRF-E (Lew et al, 1991). A previous report indicated that the GAS element of the GBP promoter could function independently of IRF-E in the IFN-g response of GBP gene (Lew et al, 1991).…”

“…The partial GBP induction by IFN-g could be attributable to activated STAT1, which binds to the GAS element overlapping with the IRF-E (Lew et al, 1991). A previous report indicated that the GAS element of the GBP promoter could function independently of IRF-E in the IFN-g response of GBP gene (Lew et al, 1991). Although the GAS element and STAT1 are also required for the IFN-g induction of the CIITA Type IV promoter (Muhlethaler-Mottet et al, 1998;Piskurich et al, 1999), recent evidence indicates that the CIITA Type IV promoter activation is more dependent on the IRF-E than the GAS element (Piskurich et al, 1999).…”

“…GBP promoter reporter construct The human GBP promoter reporter construct, hGBP-Luc, which contains 7216 to +19 region of the human GBP promoter (Lew et al, 1991) upstream of a luciferase gene cloned into pGEM-1 vector (Promega), was kindly provided by Tetsuya Yamagata (University of Tokyo).…”

“…Both IRF-1 and IRF-2, as well as other IRF family members, exert their transcriptional regulatory activity through binding to the highly conserved interferonresponse element (IRF-E) found in the promoters of various IFN-inducible genes, including the genes for IFN-a/b (Fujita et al, 1988;Taniguchi et al, 1997), 2'-5'-OAS (Benech et al, 1987), GBP (Lew et al, 1991;Briken et al, 1995), iNOS (Xie et al, 1993;Spink and Evans, 1997), MHC class I (Blanar et al, 1989;Chang et al, 1992), TAP1 Min et al, 1996;White et al, 1996), IL-4 (Li-Weber et al, 1994), IL-6 (Faggioli et al, 1997), and IL-7 (Aragane et al, 1997). The IRF-E is also found in the promoters of three constitutively expressed genes: EBNA1 (Schaefer et al, 1997), histone H4 (Vaughan et al, 1995(Vaughan et al, , 1998, and murine muscle VCAM-1 (Jesse et al, 1998), which are activated by IRF-2.…”

Cooperative activity between HER oncogenes and the tumor suppressor IRF-1 results in apoptosis

“…Therefore, a number of promoters containing IRF-1 speci®c binding sites were tested for activation by IRF-1 and/or HER1. A construct containing a GAS (g-interferon activated sequence) element and the ISRE (interferon stimulated response Cooperation of HER and IRF-1 S Kirchhoff and H Hauser element) of the human GBP promoter (Lew et al, 1991; Figure 4a) was made. In addition, another promoter construct containing the consensus sequence of an ISRE (interferon stimulated regulatory element, Figure 4b) alone was used.…”