The activity of interleukin-4 receptor alpha-chain promoter is regulated by a GT box element

Mol Immunol. 2006 Apr;43(11):1808-16. doi: 10.1016/j.molimm.2005.10.016. Epub 2005 Dec 7.

Abstract

Interleukin-4 receptor (IL-4R) is the cell surface complex through which interleukin-4 (IL-4) signals exert its critical biological effects. The alpha-chain of IL-4R is responsible for the high affinity binding of IL-4. In this report, is characterized, the 5' untranslated flanking region of murine IL-4Ralpha gene in the Th2 clone D10.G4.1. We have analyzed a DNA fragment spanning from -995 to +84 relative to the transcription start point. Mutagenesis analysis shows that, neither the previously described Stat6 (-395) nor the NFAT (-266) and NFkappaB (+25) sequences localized here, are involved in the IL-4Ralpha promoter activity. Reporter assays demonstrate that maximum transcriptional activity is achieved by the -89 to +84 sequence and this activity is independent of a TATA-like box located at -25. We have identified a GT box located at -45 as the critical element for the IL-4Ralpha promoter activity. Experiments in SL2 cells, which lack endogenous Sp proteins, show that IL-4Ralpha minimal promoter is transactivated by proteins of Sp family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Flanking Region / genetics
  • 5' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Gene Expression Regulation / genetics*
  • Mice
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-4 / genetics*
  • Receptors, Interleukin-4 / metabolism
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Response Elements / genetics
  • STAT6 Transcription Factor / metabolism
  • Sp1 Transcription Factor / metabolism
  • Transcription Initiation Site

Substances

  • 5' Untranslated Regions
  • NF-kappa B
  • NFATC Transcription Factors
  • RNA, Messenger
  • Receptors, Interleukin-4
  • STAT6 Transcription Factor
  • Sp1 Transcription Factor