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,Shuqin Sun,Jing An,Shude Yang,Li Li,Qing Lv,Yan Liu,Xiaojie Wu,Guiwu Qu,Tao Hu,Boqing Li,Jiangnan Xue,Xiaoli He,Xiaoshu Zhang

doi:10.18632/aging.101475

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.

Highlights

Human leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, known as CD305), is an immunoinhibitory receptor for collagen and C1q complement component [1, 2]
Analysis of luciferase activities of pGL-lair1-p7 (-162/-8), pGL-lair1-p8 (-93/8), and pGL-lair1-p9 (-43/-8), demonstrates the possible www.aging‐us.com presence of one positive regulatory element and one negative regulatory element at the -93 to -43, and -162 to -93 regions, respectively. These results indicate that pGL-lair1-p6 (-256/-8) has the basic promoter activity, that the minimal promoter of the LAIR-1 gene may be located at the -256 to -8 region relative to translational start site (TSS), and that this region possibly contains one negative and two positive regulatory elements
We determined that a DNA sequence located in the 256 to -8 region relatives to the TSS of LAIR-1 gene has basic promoter activity, which can be regulated by ETS transcription factors ELF-1, ETV-4, ETV-3L, ETS-1 and ETS-2

Summary

Introduction

Human leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1, known as CD305), is an immunoinhibitory receptor for collagen and C1q complement component [1, 2]. LAIR-1 is a 32-kDa transmembrane glycoprotein containing a single extracellular C2-type Ig-like domain and two immune receptor tyrosine-based inhibitory motifs (ITIMs) (VTYAQL and ITYAAV) in its cytoplasmic tail. LAIR-1 is structurally related to several other inhibitory immunoglobulin superfamily members, including human KIRs, human FcRa and immunoglobulin-like transcripts (ILTs), all of which are localized to the leukocyte receptor complex (LRC) on human chromo-some 19q13.4 [3]. LAIR-1 is expressed by almost all immune cells, including NK cells, 70–80% CD4+T cells, 80– 90% CD8+T cells, B cells, dendritic cells (DCs), monocytes and CD34+ hematopoietic progenitor cells. The mechanism of LAIR-1 gene regulation is still unknown

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Conclusion