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Cutting Edge: GATA-3-Dependent Enhancer Activity in IL-4 Gene Regulation

1998; American Association of Immunologists; Volume: 161; Issue: 8 Linguagem: Inglês

10.4049/jimmunol.161.8.3822

1550-6606

Sheila Ranganath, Wenjun Ouyang, Deepta Bhattarcharya, William C. Sha, Andrew Grupe, Gary Peltz, Kenneth M. Murphy,

interferon and immune responses

Abstract Previously, we analyzed the proximal IL-4 promoter in directing Th2-specific activity. An 800-base pair proximal promoter conferred some Th2-selective expression in transgenic mice. However, this region directed extremely low reporter mRNA levels relative to endogenous IL-4 mRNA, suggesting that full gene activity requires additional enhancer elements. Here, we analyzed large genomic IL-4 regions for enhancer activity and interaction with transcription factors. The proximal IL-4 promoter is only moderately augmented by GATA-3, but certain genomic regions significantly enhanced GATA-3 promoter transactivation. Some enhancing regions contained consensus GATA sites that bound Th2-specific complexes. However, retroviral transduction of GATA-3 into developing T cells induced IL-5 to full Th2 levels, but only partially restored IL-4 production. Thus, we propose that GATA-3 is permissive, but not sufficient, for full IL-4 enhancement and may act through GATA elements surrounding the IL-13/IL-4 gene locus.