Interferon regulatory factor-2 directs transcription from the gp91phox promoter.
Repressor elements in the gp91(phox) promoter are necessary to restrict tissue-specific transcription to mature phagocytes. Deletion of these elements leads to significant promoter activity in cell lines such as HEL and K562 that do not normally express gp91(phox). The -100 to +12 base pair gp91(phox) promoter region is sufficient to direct maximal de-repressed transcription in these cells. However, promoter activity is dramatically decreased following a 16-base pair truncation that deletes an interferon-stimulated response element. This element interacts with IRF-1 and IRF-2, members of the interferon regulatory factor family of transcription factors. In addition, this promoter region is bound by a factor with properties similar to BID, a DNA-binding protein that also interacts with three upstream sites within the gp91(phox) promoter. Transient transfection studies using mutated promoters indicate that both the IRF and BID binding sites are required for maximal gp91(phox) promoter activity. Overexpression of IRF-1 or IRF-2 in K562 cells leads to transactivation of gp91(phox) promoter constructs, which is dependent on the presence of an intact IRF binding site. IRF-2 predominates in macrophages that express the gp91(phox) gene as well as in HEL and K562 cells. We conclude that IRF-2 and BID activate gp91(phox) promoter activity in the absence of transcriptional repression.
Luo
W
W
Herman B. Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5225, USA.
Skalnik
D G
DG
D001665:Binding Sites; D002454:Cell Differentiation; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D008562:Membrane Glycoproteins / Q000235:genetics*; D008957:Models, Genetic; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis; D012097:Repressor Proteins; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases