Synergism between distinct enhanson domains in viral induction of the human beta interferon gene.

Abstract

This study demonstrates distinct virus-inducible enhanson properties for three regions of the human beta interferon (IFN-,B) promoter; maximum vrus inducibility required syngerism among all three enhansons. Expression of the ERF-1 transcription factor differentially increased the expression of plasmids containing (AAGTGA)4 or PRDM (-94 to -78) motifs but was inefficient in the induction of the intact IFN-0 promoter.The human T-cell (11,14,38,41). The contribution of an individual enhanson to overall enhancer activity may vary in a cellspecific manner, reflecting the relative abundance and/or activity of specific transcription factors. Four distinct classes of enhansons have been described. Class A enhansons display strict spacing requirements and exhibit enhancer activity when tandem repeats of the motif are oligomerized. Class B enhansons exhibit no enhancer activity when multimerized on their own but can generate enhancer activity when juxtaposed with class A motifs (to form a proto-enhancer) and then oligomerized. Class C enhansons possess intrinsic proto-enhancer activity and, when oligomerized, form a functional enhancer element without strict spacing requirements between enhansons. Class D enhansons, exemplified by steroid response elements, display enhancer activity once the receptor is bound (14,31,36,41).Virus-induced activation of beta interferon (IFN-P) transcription is mediated by the interaction of regulatory proteins with enhanson elements in the IFN-1 promoter. In particular, a hexameric sequence, AAGTGA, permutations of which are present throughout the IFN-P promoter between -107 and -65 relative to the mRNA start site, can function as a virus-inducible or constitutive enhancer when present in tandem repeats (12,20). Multimers of the AAGTGA hexamer generate the sequence GAAAGT, which * Corresponding author.is thought to represent a high-affinity site for two DNAbinding proteins, 18,19,26,39). Recently, different types of (GAAANN)4 sequences mediating virus inducibility have been described, indicating that different hexameric sequences are not equivalent and that other IRF-like proteins are involved in alpha interferon and IFN-,B induction (37).The natural IFN-P promoter contains an interferon regulatory element (located at -77 to -37) which includes two positive regulatory domains (PRDI and PRDII) and one negative regulatory domain, as defined by mutational analysis and protein-DNA interactions (21,22,33,48,49). The PRDI domain (-77 to -64) is thought to interact with the IRF proteins (19,26,39,48), as well as with other constitutive and inducible factors (33,37,48). The PRDII domain (5'-GGGAAATTCC-3'; -64 to -55) binds NF-KB, a cellular factor involved in the transcriptional activation of several viral and cellular genes (3,6,30,32,40,43 (16,28,34,46

Regulation of interferon responses in medulloblastoma cells by interferon regulatory factor-1 and -2

“…No detectable production of IFN-f in RI cells after IFN treatment was in agreement with results in stable transfectants overexpressing IRF-1 derived from other cell types (Leblanc et al, 1990;Reis et al, 1992). Under viral induction, RI and R2 cells produced 2.46-and 2.24-fold higher IFN-f than C-76 cells, and under poly(I): poly(C) stimulation after IFN-P priming, RI and R2 cells produced 2.33-and 1.87-fold higher IFN-P than C-76 cells respectively (Table 1).…”

An ATF/CREB binding site is required for virus induction of the human interferon beta gene [corrected]

“…6D). Thus, the transcription factors that are responsible for inducible activ- (7,11,39). The combination of these elements in the HuIFN-,Bpromoter…”

“…The positive regulatory domain I (PRDI) is located between nucleotides -77 and -64 from the start site of transcription, while another element (PRDII) is located between -66 and -55 (7)(8)(9)(10). A third element (PRDIII) is located between -90 and -78 (11)(12)(13)(14)(15).…”

Endothelial Interferon Regulatory Factor 1 Cooperates with NF-κB as a Transcriptional Activator of Vascular Cell Adhesion Molecule 1

“…This finding is consistent with other observations showing that overexpressed IRF-1 can superinduce target gene expression induced by exogenous stimuli. Leblanc et al (35) demonstrated that IRF-1 could superinduce phorbol ester-mediated activation of an IFN-␤ promoter/reporter construct. Reis et al (58) studied cells stably overexpressing IRF-1 and observed superinduced levels of endogenous IFN-␤ when transfected cells were stimulated by either poly(I)-poly(C) or virus.…”

“…Full-length cDNAs encoding p50, HMGI, and IRF-1 were cloned in frame to glutathione S-transferase (GST)-expressing plasmids (13). GST alone or its fusion derivatives immobilized to glutathione-agarose beads were incubated with in vitro-translated 35 S-labeled proteins for 2 h at 4ЊC in binding buffer (150 mM NaCl, 10 mM Tris [pH 8.0], 0.2% Nonidet P-40, 0.2% BSA) and then washed three times with binding buffer and once with binding buffer but without BSA. Interactions were analyzed by SDS-polyacrylamide gel electrophoresis (PAGE).…”