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DNA methylation‐mediated Siglec‐7 regulation in natural killer cells via two 5′ promoter CpG sites
Author(s) -
Huang HsinTing,
Su ShihChi,
Chiou TzeonJye,
Lin YenHsi,
Shih YiChen,
Wu YuXuan,
Fan TingHsi,
Twu YuhChing
Publication year - 2020
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13179
Subject(s) - siglec , cpg site , dna methylation , biology , microbiology and biotechnology , epigenetics of physical exercise , dna methyltransferase , nkg2d , gene expression , gene , cytotoxic t cell , biochemistry , lectin , in vitro
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.