Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level

Immunity. 2001 Apr;14(4):447-59. doi: 10.1016/s1074-7613(01)00125-x.


Using a transgenic approach, we examined distal regulatory elements located in the IL-4 locus and the role of GATA-3 at these elements. The intergenic DNase I hypersensitive sites (HSS) showed strong enhancement, and the intronic enhancer (IE) and HS5/HS5a sites showed weaker enhancement of the IL-4 promoter. Elements in the 3' region of the IL-4 gene contributed to Th2 specificity. All individual enhancers were T cell activation dependent but not Th2 specific, with the exception of IE. However, when these distal elements were combined into a "minilocus," expression was strongly enhanced and Th2 specific. GATA-3 mediated strong enhancement of IL-4 promoter activity in Th1 cells when the promoter was embedded in the minilocus or linked to HSS and IE, demonstrating that GATA-3 acts through these elements to regulate IL-4 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / metabolism*
  • DNA, Intergenic
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic
  • GATA3 Transcription Factor
  • Gene Expression Regulation
  • Genes, Reporter
  • Interleukin-4 / genetics*
  • Introns
  • Luciferases / genetics
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid*
  • Trans-Activators / metabolism*
  • Transcription, Genetic


  • Chromatin
  • DNA, Intergenic
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Trans-Activators
  • Interleukin-4
  • Luciferases