CUTTING EDGE - GATA-3-DEPENDENT ENHANCER ACTIVITY IN IL-4 GENE-REGULATION

Previously, we analyzed the proximal IL-4 promoter in directing Th2-sp ecific activity. An 800-base pair proximal promoter conferred some Th2 -selective expression in transgenic mice. However, this region directe d extremely low reporter mRNA levels relative to endogenous IL-4 mRNA, suggesting that full gene activity requires additional enhancer eleme nts. Here, we analyzed large genomic IL-4 regions for enhancer activit y and interaction with:transcription factors. The proximal IL-4 promot er is only moderately augmented by GATA-3, bet certain genomic regions significantly enhanced GATA-3 promoter transactivation, Some enhancin g regions contained consensus GATA sites that bound Th2-specific compl exes. However, retroviral transduction of GATA-3 into developing T cel ls induced IL-5 to full Th2 levels, but only partially restored IL-4 p roduction. Thus,we propose that GATA-3 Is permissive, hut not sufficie nt, for full IL-4 enhancement and may act through GATA elements surrou nding the IL-13/IL-4 gene locus.