CCAAT displacement protein competes with multiple transcriptional activators for binding to four sites in the proximal gp91phox promoter.
CCAAT displacement protein (CDP) competes with transcriptional activating proteins for binding to each of four elements within the myeloid-specific gp91(phox) promoter. CDP exhibits the strongest affinity for a site centered at -110 base pairs (bp) of the promoter and progressively weaker affinities for three more distal binding sites. CDP binding to each site is down-regulated during terminal phagocytic differentiation, coincident with induction of gp91(phox) expression. Deletion of the high affinity CDP-binding site at -110 bp leads to inappropriate gp91(phox) promoter activity in HeLa, K562, and HEL cells. An overlapping binding site for the CCAAT box-binding factor CP1 is required for derepressed promoter activity in HeLa and K562 cells, but is dispensable in HEL cells, indicating that different cell types require distinct cis-elements for gp91(phox) promoter activity. Derepressed gp91(phox) promoter activity is further increased upon removal of a second CDP-binding site centered at -150 bp, revealing that CDP represses gp91(phox) expression via multiple cis-elements. We present a model in which restriction of gp91(phox) expression to mature myeloid cells involves competition between transcriptional activators and repressors for binding to multiple sites within the promoter.
Luo
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Herman B Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5225, USA.
Skalnik
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DG
D001665:Binding Sites; D001667:Binding, Competitive; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells; D018398:Homeodomain Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
C080632:CUX1 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases