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  • Title: Overexpression of CCAAT displacement protein represses the promiscuously active proximal gp91(phox) promoter.
    Author: Catt D, Hawkins S, Roman A, Luo W, Skalnik DG.
    Journal: Blood; 1999 Nov 01; 94(9):3151-60. PubMed ID: 10556202.
    Abstract:
    CCAAT displacement protein (CDP) is a transcriptional repressor that restricts expression of the gp91(phox) gene to mature myeloid cells. CDP interacts with multiple sites within the -450 to +12 bp human gp91(phox) promoter, and down-regulation of CDP DNA-binding activity is required for induction of gp91(phox) transcription in mature phagocytes. Truncation of the gp91(phox) promoter to -102 to +12 bp removes 4 CDP-binding sites and reveals a promiscuous promoter activity that is active in some nonphagocytic cells. A cis-element at -90 bp is required for derepressed transcription and serves as a binding site for multiple transcriptional activators. We now report that this element also serves as a binding site for CDP. The affinity of CDP for this element is relatively weak compared with upstream CDP-binding sites within the promoter, consistent with the promiscuous transcriptional activity exhibited by the -102 to +12 bp gp91(phox) promoter fragment. Further analysis of the proximal promoter reveals an additional weak-affinity CDP-binding site centered at approximately -20 bp. Overexpression of cloned CDP represses the -102 to +12 bp gp91(phox) promoter, indicating that these proximal CDP-binding sites are functionally significant. The constellation of transcriptional activators and a repressor that interacts with the -90 bp cis-element is identical to that observed for a promoter element at -220 bp, reflecting the highly modular organization of the gp91(phox) promoter. These studies illustrate the complex interplay between transcriptional activators and a repressor that contribute to the myeloid-restricted expression of the gp91(phox) gene.
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