The human KIR genes encode a family of class I MHC receptors that are expressed on subsets of NK cells. The expression of KIR proteins is controlled by a stochastic process, and competition between sense and antisense promoter elements has been suggested to program the variegated expression of these genes. Previous studies have demonstrated distinct roles of distal, intermediate, and proximal sense promoter/enhancer elements in gene activation and expression. Conversely, proximal and intronic antisense promoter transcripts have been associated with gene silencing at different stages of NK cell development. In the current study, we examine the effect of intermediate promoter deletion on KIR2DL1 expression in the YTS cell line. Homozygous deletion of the KIR2DL1 intermediate element did not affect proximal promoter activity but resulted in increased detection of upstream transcripts. No significant changes in alternative mRNA splicing or expression levels of KIR2DL1 protein were observed. However, intermediate element deletion was associated with a reduced frequency of gene activation by 5-azacytidine. Taken together, these results indicate that the intermediate element is not an enhancer required for KIR expression; however, it is required for the efficient activation of the gene.

人类KIR基因编码 I 类 MHC 受体家族，这些受体在 NK 细胞亚群上表达。KIR 蛋白的表达受随机过程控制，有义和反义启动子元件之间的竞争已被建议来编程这些基因的多样化表达。先前的研究已经证明远端、中间和近端有义启动子/增强子元件在基因激活和表达中的不同作用。相反，近端和内含子反义启动子转录本与 NK 细胞发育不同阶段的基因沉默相关。在当前的研究中，我们检查了中间启动子缺失对 YTS 细胞系中 KIR2DL1 表达的影响。KIR2DL1中间元件的纯合删除不会影响近端启动子活性，但会导致上游转录本的检测增加。没有观察到选择性 mRNA 剪接或 KIR2DL1 蛋白表达水平的显着变化。然而，中间元件缺失与 5-氮杂胞苷激活基因的频率降低有关。综上所述，这些结果表明中间元件不是 KIR 表达所需的增强子；然而，它是基因有效激活所必需的。