Journal
IMMUNITY
Volume 14, Issue 4, Pages 447-459Publisher
CELL PRESS
DOI: 10.1016/S1074-7613(01)00125-X
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Using a transgenic approach, we examined distal regulatory elements located in the 1L-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-9 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.
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