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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >DNA methylation‐mediated Siglec‐7 Siglec‐7 regulation in natural killer cells via two 5′ promoter CpG sites
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DNA methylation‐mediated Siglec‐7 Siglec‐7 regulation in natural killer cells via two 5′ promoter CpG sites

机译:DNA甲基化介导的SIGLEC-7 SIGLEC-7通过两种5'启动子CPG位点的天然杀伤细胞中的调节

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Summary 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.
机译:发明内容首次在天然杀伤(NK)细胞上发现,已知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)用于调节许多重要的生物活性。然而,NK细胞中SigleC-7表达的细节调节机制目前仍不清楚。在这项研究中,我们旨在研究细胞表面SigleC-7的表达如何调节,发现,在NK细胞系和外周NK细胞中,转录是主要的调节步骤。此外,当用DNA甲基转移酶(DNMT)抑制剂(DNMT)抑制剂处理NK-92MI和外周NK细胞,用9个CPG位点进行CPG岛,在5'SigleC-7启动子中变得明显脱甲基化,并且SIGLEC-7表达在RNA转录物中增加和表面蛋白质。在该CPG岛内,我们将CPG 8和CPG 9识别为两个关键调节器,负责SigleC-7表达式。另外,通过使用组蛋白脱乙酰酶(HDAC)抑制剂,丁酸,我们表明SIGLEC-7表达也经受组蛋白改性。与5-氮杂胞苷和丁酸的组合治疗对外周NK细胞中的SigleC-7转录物表达表达了一种添加剂影响。

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