Ranganath S, Ouyang W, Bhattarcharya D, Sha W C, Grupe A, Peltz G, Murphy K M
Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 1998 Oct 15;161(8):3822-6.
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.
此前，我们分析了近端白细胞介素4（IL-4）启动子指导Th2特异性活性的情况。一个800碱基对的近端启动子在转基因小鼠中赋予了一些Th2选择性表达。然而，相对于内源性IL-4 mRNA，该区域指导的报告基因mRNA水平极低，这表明完整的基因活性需要额外的增强子元件。在此，我们分析了大片段基因组IL-4区域的增强子活性以及与转录因子的相互作用。近端IL-4启动子仅被GATA-3适度增强，但某些基因组区域显著增强了GATA-3启动子的反式激活。一些增强区域含有与Th2特异性复合物结合的共有GATA位点。然而，将GATA-3逆转录病毒转导至发育中的T细胞中可诱导白细胞介素5（IL-5）达到完全的Th2水平，但仅部分恢复IL-4的产生。因此，我们提出GATA-3对于完全增强IL-4是允许的，但并不充分，并且可能通过IL-13/IL-4基因座周围的GATA元件发挥作用。
