DNA methylation‐mediated Siglec‐7 regulation in natural killer cells via two 5′ promoter CpG sites

Autor:	Shih Chi Su, Yu Xuan Wu, Yuh Ching Twu, Yi Chen Shih, Tzeon Jye Chiou, Hsin Ting Huang, Ting Hsi Fan, Yen Hsi Lin
Rok vydání:	2020
Předmět:	0301 basic medicine Transcription Genetic Immunology Antigens Differentiation Myelomonocytic DNA methyltransferase Histone Deacetylases Cell Line Epigenesis Genetic Natural killer cell 03 medical and health sciences 0302 clinical medicine Transcription (biology) Lectins medicine Humans Immunology and Allergy RNA-Seq Epigenetics Promoter Regions Genetic biology Chemistry SIGLEC Original Articles DNA Methylation respiratory system Cell biology Histone Code Histone Deacetylase Inhibitors Killer Cells Natural 030104 developmental biology medicine.anatomical_structure Histone CpG site DNA methylation Azacitidine biology.protein Butyric Acid CpG Islands 030215 immunology
Zdroj:	Immunology
ISSN:	1365-2567 0019-2805
DOI:	10.1111/imm.13179
Popis:	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.
Databáze:	OpenAIRE
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