title: CCAAT displacement protein competes with multiple transcriptional activators for binding to four sites in the proximal gp91phox promoter.
abstract: 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.
authors.affiliation: Herman B Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5225, USA.
authors.forename: W
authors.initials: W
authors.lastname: Luo
authors.forename: D G
authors.initials: DG
authors.lastname: Skalnik
mesh_terms: 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
chemical_list: 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