Regulation of the human Fc epsilon RI alpha-chain distal promoter

J Immunol. 2003 Apr 1;170(7):3732-8. doi: 10.4049/jimmunol.170.7.3732.

Abstract

The alpha-chain of the high affinity receptor for IgE (Fc epsilon RI) is essential for cell surface expression of Fc epsilon RI and binding of the IgE Ab. The human alpha-chain gene possesses two promoters: the proximal promoter, which is highly conserved with that of rodent; and the distal promoter, the structure and role of which are largely unknown. Transcriptional regulation of the alpha-chain distal promoter was investigated in this study. Transient reporter assay revealed critical region for transcription activity located within -27/-17. EMSA identified Elf-1, YY1, and PU.1 as transcription factors binding to this region. In contrast to the proximal promoter, which was trans-activated by YY1 and PU.1, these transcription factors exhibited repressive function on this promoter. Addition of IL-4 caused a marked increase in transcription from the distal promoter and subsequently increased the intracellular production of the alpha-chain. These results indicate that IL-4-dependent up-regulation of the human alpha-chain was due to enhancement of distal promoter activity and suggests that the two promoters have different regulatory mechanisms for alpha-chain expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Erythroid-Specific DNA-Binding Factors
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Interleukin-4 / pharmacology
  • Molecular Sequence Data
  • Promoter Regions, Genetic / immunology*
  • Proto-Oncogene Proteins / isolation & purification
  • Proto-Oncogene Proteins / metabolism
  • Receptors, IgE / antagonists & inhibitors
  • Receptors, IgE / genetics*
  • Receptors, IgE / metabolism*
  • Regulatory Sequences, Nucleic Acid / immunology
  • Repressor Proteins / isolation & purification
  • Repressor Proteins / metabolism
  • Repressor Proteins / physiology
  • Trans-Activators / isolation & purification
  • Trans-Activators / metabolism
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism
  • Transcription Initiation Site
  • Tumor Cells, Cultured
  • YY1 Transcription Factor

Substances

  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • Proto-Oncogene Proteins
  • Receptors, IgE
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • YY1 Transcription Factor
  • YY1 protein, human
  • proto-oncogene protein Spi-1
  • Interleukin-4