title: Differential transcription factor use by the KIR2DL4 promoter under constitutive and IL-2/15-treated conditions.
abstract: KIR2DL4 is unique among human KIR genes in expression, cellular localization, structure, and function, yet the transcription factors required for its expression have not been identified. Using mutagenesis, EMSA, and cotransfection assays, we identified two redundant Runx binding sites in the 2DL4 promoter as essential for constitutive 2DL4 transcription, with contributions by a cyclic AMP response element (CRE) and initiator elements. IL-2- and IL-15-stimulated human NK cell lines increased 2DL4 promoter activity, which required functional Runx, CRE, and Ets sites. Chromatin immunoprecipitation experiments show that Runx3 and Ets1 bind the 2DL4 promoter in situ. 2DL4 promoter activity had similar transcription factor requirements in T cells. Runx, CRE, and Ets binding motifs are present in 2DL4 promoters from across primate species, but other postulated transcription factor binding sites are not preserved. Differences between 2DL4 and clonally restricted KIR promoters suggest a model that explains the unique 2DL4 expression pattern in human NK cells.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Presnell
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Corrin N
authors.initials: CN
authors.lastname: Chlebowy
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Attar
authors.forename: Charles T
authors.initials: CT
authors.lastname: Lutz
mesh_terms: D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054345:Receptors, KIR2DL4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020218:Response Elements / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics / Q000276:immunology
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C494041:ETS1 protein, human; C569274:IL15 protein, human; C508594:IL2 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; C515079:KIR2DL4 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D054345:Receptors, KIR2DL4; C493729:Runx3 protein, human