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

Hsin Ting Huang, Shih Chi Su, Tzeon Jye Chiou, Yen Hsi Lin, Yi Chen Shih, Yu Xuan Wu, Ting Hsi Fan, Yuh Ching Twu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)38-51
Number of pages14
JournalImmunology
Volume160
Issue number1
DOIs
Publication statusPublished - May 1 2020

Keywords

  • DNA methylation
  • epigenetics
  • histone acetylation
  • natural killer cell
  • Siglec-7

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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