Identification of bidirectional promoters in the human KIR genes
Identification of bidirectional promoters in the human KIR genes
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DOI：
10.1038/sj.gene.6364381
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发表时间：
2007-04-01
影响因子：
5
通讯作者：
Anderson, S. K.
中科院分区：
文献类型：
--
作者：
Davies, G. E.;Locke, S. M.;Anderson, S. K.
虽然人类和小鼠自然杀伤（NK）细胞表达的I类MHC受体具有不同的分子来源，但它们是以杂色模式表达的功能类似物。鼠Ly 49 I类受体含有双向启动子，已提出控制这些基因的概率表达。人类杀伤性Ig样受体（KIR）基因中是否存在类似的元件是一个基本问题。对分离KIR 2DL 4基因和邻近的KIR 3DL 1基因的2kb基因间区域的详细分析揭示了在人KIR基因中存在另外的启动子元件。值得注意的是，先前表征的KIR 3DL 1近端启动子具有双向启动子活性，其映射到含有CREB、AML、Sp1和Ets转录因子结合位点的88 bp DNA片段。单个KIR基因和等位基因具有不同性质的双向启动子。对KIR+和KIR-NK细胞和NK前体的分析表明，在缺乏KIR蛋白表达的细胞中发现了来自双向启动子的逆转录，但在表达KIR的成熟NK细胞中不存在，这表明来自近端启动子的逆转录阻断了未成熟NK和前体细胞中的基因活化。
Although the class I MHC receptors expressed by human and mouse natural killer (NK) cells have distinct molecular origins, they are functional analogues that are expressed in a variegated pattern. The murine Ly49 class I receptors contain bidirectional promoters that have been proposed to control the probabilistic expression of these genes. Whether similar elements are present in the human killer Ig-like receptor (KIR) genes is a fundamental question. A detailed analysis of the 2 kb intergenic region separating the KIR2DL4 gene and the adjacent KIR3DL1 gene revealed that additional promoter elements exist in the human KIR genes. Remarkably, the previously characterized KIR3DL1 proximal promoter possesses bidirectional promoter activity that maps to an 88 bp DNA fragment containing CREB, AML, Sp1 and Ets transcription factor binding sites. Individual KIR genes and alleles possess bidirectional promoters with distinct properties. Analysis of KIR+ and KIR- NK cells and NK precursors indicates that reverse transcripts from the bidirectional promoter are found in cells that lack KIR protein expression, but are not present in mature KIR- expressing NK cells, suggesting that reverse transcription from the proximal promoter blocks gene activation in immature NK and precursor cells.