Functional redundancy of transcription factor-binding sites in the killer cell Ig-like receptor (KIR) gene promoter.
Functional redundancy of transcription factor-binding sites in the killer cell Ig-like receptor (KIR) gene promoter.
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杀伤细胞 Ig 样受体 (KIR) 基因启动子中转录因子结合位点的功能冗余。
DOI：
10.1093/intimm/dxl043
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Lutz,CharlesT
中科院分区：
文献类型：
--
作者：
Presnell,StevenR;Zhang,Lei;Ramilo,CeciliaA;Chan,Huei-Wei;Lutz,CharlesT
Variegated expression of inhibitory killer cell Ig-like receptors (KIRs) for MHC class I molecules helps NK cells distinguish normal from aberrant self and avoid autoreactivity. Prior studies ofKIRpromoters have produced conflicting results and nocis-acting sites have been independently confirmed. We took a comprehensive linker-scanning mutagenesis approach and substituted 24 consecutive 10-bp segments in the humanKIR3DL1promoter. Our analysis revealed eight segments that activated and three segments that repressedKIRtranscription. Site-directed mutagenesis and electrophoretic mobility shift assays indicated that optimalKIRtranscription requires a proximal Ets site that binds several Ets family members, a cAMP response element (CRE), a Runx site and a site that mediates complex interactions between Ets family members, signal transducer and activator of transcription 5 (STAT5) and YY1; Sp1 also contributes toKIRtranscription.KIRtranscription was greatly reduced by several compound mutations and was abrogated by a combination of mutations that affected the proximal Ets site, and the CRE, Runx, Sp1 and Ets/STAT sites. The many transcription factors that contribute toKIRtranscription are partially redundant in the setting of transient transfection assays, helping to explain why only 0–2 activating sites had been reported in each of three prior studies. We propose that the multiplicity of transcription factors enables NK cells to sustain continuousKIRexpression in diverse cellular and cytokine milieus, thus preventing NK autoreactivity.
