Characterization of a gp91-phox promoter element that is required for interferon gamma-induced transcription.
The cytochrome b558 heavy chain (gp91-phox) is expressed nearly exclusively in terminally differentiating myelomonocytic cells, thereby providing a model to study the events of late myeloid differentiation. We describe a tissue culture assay for studying interferon gamma induction of gp91-phox expression and a cis-element in the gp91-phox promoter that is necessary but not sufficient for this activity. In vitro assays reveal two DNA-binding proteins that interact with this cis-element. One factor is restricted to hematopoietic cells, is required for an interferon gamma response, and binds to an element similar to the Ets protein family consensus, although it does not correspond to known family members. The second factor is the ubiquitous CCAAT-binding protein CP1, which is dispensable for an interferon gamma response. Single base pair mutations in the gp91-phox promoter that specifically abolish the binding of the hematopoietic-associated factor have previously been identified in chronic granulomatous disease patients (Newburger, P. E., Skalnik, D. G., Hopkins, P. J., Eklund, E. A., and Curnutte, J. T. (1994) J. Clin. Invest. 94, 1205-1211). The data reported here directly demonstrate the functional significance of the hematopoietic-associated factor for gp91-phox promoter activity and reveal the binding properties and tissue distribution of this novel DNA-binding protein.
Eklund
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EA
Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202-5225, USA.
Skalnik
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DG
D001483:Base Sequence; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases