TY - JOUR
T1 - Differential transcription factor use by the KIR2DL4 promoter under constitutive and IL-2/15-treated conditions
AU - Presnell, Steven R.
AU - Zhang, Lei
AU - Chlebowy, Corrin N.
AU - Al-Attar, Ahmad
AU - Lutz, Charles T.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84860338295&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860338295&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1103352
DO - 10.4049/jimmunol.1103352
M3 - Article
C2 - 22467658
AN - SCOPUS:84860338295
SN - 0022-1767
VL - 188
SP - 4394
EP - 4404
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -