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

Aging (Albany NY). 2018 Jun 18;10(6):1390-1401. 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.

Keywords: ETS transcription factors; ETS-2; LAIR-1; Luciferase; promoter; transfection.

MeSH terms

  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / metabolism
  • Ephrin-A2 / genetics
  • Ephrin-A2 / metabolism
  • Gene Expression Regulation / physiology
  • HEK293 Cells
  • Humans
  • Promoter Regions, Genetic
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / metabolism
  • Proto-Oncogene Protein c-ets-2 / genetics
  • Proto-Oncogene Protein c-ets-2 / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / metabolism*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Up-Regulation

Substances

  • Adenovirus E1A Proteins
  • ETS1 protein, human
  • ETS2 protein, human
  • ETV3 protein, human
  • ETV4 protein, human
  • Ephrin-A2
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Receptors, Immunologic
  • leukocyte-associated immunoglobulin-like receptor 1