Regulation by PU.1 of CYBB Expression

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Phagocyte NADPH oxidase makes superoxide anion which is essential for microbial killing and is expressed on the surface of mature neutrophils. eosinophils, monocytes/macrophages and B lymphocytes. It is a multi-component cnzymes and contains gp9lphox, a flavo-heme protein, which is encoded in CYBB on X chromosome. Abnormalities of this gene, therefore, occupy more than 70% of NADPH oxidase deficiency called chronic granulomatous disease. We rcccntly discovered a CGD patient with phenotypically normal eosinophils, and suggested certain mechnisrn particular to neutrophils, monocytes and B lymphocytes : Analysis of promoter sequence revealed a C to T point mutation at -53 of CYBB Electrophoresis mobility shift assays exhibited PU.1 and hematopoietic associated factor-l(HAF-1) as the binding proteins whose binding is sensitive to this mutation. We discovered -56G and -50G mutations to fail in binding to only HAF-1 and PU.1, respectively. The latter mutation but not the former one decreased the promoter activity as -53T mutation. Accordingly these results indicate PU.l, but not HAF-1, to be essential for the expression of CYBB in neutrophils, monocytes, and B lymphocytes. Interaction of PU.1 with transcriptional modulators are now under experiments. PU.1 is also detectable in eosinophils, and may have a significant role in the cells for CYBB activation, even if it is not essential. In addition, we found GATA-3 to be ensinophil-specific repressor of CYBB.