Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level.
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.
Lee
G R
GR
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Fields
P E
PE
Flavell
R A
RA
D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D015847:Interleukin-4 / Q000235:genetics*; D007438:Introns; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D008156:Luciferases