First discovered on the natural killer (NK) cell, the cell surface inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is known for regulating many important biological activities. However, the detail regulatory mechanism for Siglec-7 expression in NK cells currently remains unclear. In this study, we aimed to investigate how cell surface Siglec-7 expression is regulated and found that, in both NK cell lines and peripheral NK cells, transcription was the main regulatory step. Furthermore, when NK-92MI and peripheral NK cells were treated with DNA methyltransferase (DNMT) inhibitor, the CpG island, with 9 CpG sites, in 5' Siglec-7 promoter became noticeably hypomethylated, and Siglec-7 expression increased in both RNA transcript and surface protein. Within this CpG island, we identified both CpG 8 and CpG 9 as two key regulators responsible for Siglec-7 expression. Additionally, by using histone deacetylases (HDAC) inhibitor, butyric acid, we showed that Siglec-7 expression was also subjected to the histone modification. And a combined treatment with both 5-azacytidine and butyric acid showed an additive effect on Siglec-7 transcript expression in peripheral NK cells.

中文翻译：

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通过两个5'启动子CpG位点在自然杀伤细胞中进行DNA甲基化介导的Siglec-7调控。

最早发现于自然杀伤（NK）细胞上的细胞表面抑制受体唾液酸结合免疫球蛋白样凝集素7（Siglec-7）可调节许多重要的生物学活性。然而，目前尚不清楚NK细胞中Siglec-7表达的详细调控机制。在这项研究中，我们旨在研究如何调节细胞表面Siglec-7的表达，并发现在NK细胞系和外周NK细胞中，转录都是主要的调控步骤。此外，当用DNA甲基转移酶（DNMT）抑制剂处理NK-92MI和外周血NK细胞时，具有9个CpG位点的CpG岛在5'Siglec-7启动子中明显被甲基化，并且在两个RNA转录物中Siglec-7表达均增加。和表面蛋白。在这个CpG岛内，我们确定CpG 8和CpG 9是负责Siglec-7表达的两个关键调控因子。此外，通过使用组蛋白脱乙酰基酶（HDAC）抑制剂丁酸，我们显示Siglec-7表达也经历了组蛋白修饰。5-氮杂胞苷和丁酸的联合处理对外周血NK细胞中Siglec-7转录表达有累加作用。