Research Paper Volume 10, Issue 6 pp 1390—1401

Five ETS family members, ELF-1, ETV-4, ETV-3L, ETS-1, and ETS-2 upregulate human leukocyte-associated immunoglobulin-like receptor-1 gene basic promoter activity

Qizhi Cao 1, 2, *, , Shude Yang 3, *, , Qing Lv 2, 5, *, , Yan Liu 1, , Li Li 4, , Xiaojie Wu 1, , Guiwu Qu 2, 5, , Xiaoli He 6, , Xiaoshu Zhang 1, , Shuqin Sun 5, , Boqing Li 7, , Jing An 8, , Tao Hu 1, , Jiangnan Xue 1, ,

  • 1 Department of Immunology, School of Basic Medical Sciences, Binzhou Medical University, Shandong 264003, China
  • 2 Anti-aging Research Institution, Binzhou Medical University, Shandong 264003, China
  • 3 School of Agriculture, Ludong University, Shandong 264003, China
  • 4 Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 5 School of Gerontology, Binzhou Medical University, Shandong 264003, China
  • 6 The People's Liberation Army 107 Hospital, Affiliated Hospital of Bin Zhou Medical University, Yantai 264002, China
  • 7 Department of Microbiology, School of Basic Medical Sciences, Binzhou Medical University, Shandong 264003, China
  • 8 School of Medicine, University of California - San Diego, La Jolla, CA 92037, USA
* Equal contribution

received: December 25, 2017 ; accepted: June 10, 2018 ; published: June 18, 2018 ;

https://doi.org/10.18632/aging.101475
How to Cite

Copyright: Cao et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Human leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), an immunoinhibitory receptor, is expressed on most types of hematopoietic cells and some tumor cells. LAIR-1 plays an inhibitory role in immune cell maturation, differentiation, and activation. LAIR-1 is also involved in some autoimmune diseases and tumors. However, the mechanism controlling the regulation of the LAIR-1 gene is still unknown. In order to elucidate the molecular mechanisms involved in LAIR-1 regulation, in the present study, we cloned and characterized the promoter region of LAIR-1 gene using a series of truncated promoter plasmids in luciferase reporter assays. Our results show that the basic core promoter of LAIR-1 is located within the region -256/-8 relative to the translational start site. Our further studies indicate that five ETS transcription factors: ELF-1, ETV-4, ETV-3L, ETS-1 and ETS-2, can up-regulate the LAIR-1 basic promoter activity. Of these, ETS-2 is the most effective transcription factor. Moreover, ETS-2 was confirmed to interact directly with the basic promoter of LAIR-1. This study presents the first description of regions/factors capable of up-regulation the promoter activity of LAIR-1. This new knowledge contributes to understanding of the molecular mechanisms involved in LAIR-1 associated immune regulation and diseases.

Abbreviations

LAIR-1: leukocyte-associated immunoglobulin-like receptor-1; ITIMs: immune receptor tyrosine-based inhibitory motifs; TSS: translational start site; CHIP: Chromatin Immunoprecipitation; EMSA: Electrophoretic mobility shift assays.