Multiple closely-linked NFAT/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter

Nucleic Acids Res. 1993 Dec 11;21(24):5694-704. doi: 10.1093/nar/21.24.5694.

Abstract

We show here that the immediate upstream region (from position -12 to -270) of the murine interleukin 4 (Il-4) gene harbors a strong cell-type specific transcriptional enhancer. In T lymphoma cells, the activity of the Il-4 promoter/enhancer is stimulated by phorbol esters, Ca++ ionophores and agonists of protein kinase A and inhibited by low doses of the immunosuppressant cyclosporin A. The Il-4 promoter/enhancer is transcriptionally inactive in B lymphoma cells and HeLa cells. DNase I footprint protection experiments revealed six sites of the Il-4 promoter/enhancer to be bound by nuclear proteins from lymphoid and myeloid cells. Among them are four purine boxes which have been described to be important sequence motifs of the Il-2 promoter. They contain the motif GGAAA and are recognized by the inducible and cyclosporin A-sensitive transcription factor NFAT-1. Three of the Il-4 NFAT-1 sites are closely linked to weak binding sites of Octamer factors. Several purine boxes and an AT-rich protein-binding site of the Il-4 promoter are also recognized by the high mobility group protein HMG I(Y). Whereas the binding of NFAT-1 and Octamer factors enhance the activity of the Il-4 promoter, the binding of HMG I(Y) suppresses its activity and, therefore, appears to be involved in the suppression of Il-4 transcription in resting T lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • DNA
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • High Mobility Group Proteins / metabolism*
  • Humans
  • Interleukin-4 / genetics*
  • Mice
  • Molecular Sequence Data
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Promoter Regions, Genetic*
  • T-Lymphocytes / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • Interleukin-4
  • DNA