GATA-3-dependent enhancer activity in IL-4 gene regulation.
GATA-3-dependent enhancer activity in IL-4 gene regulation.
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DOI：
10.4049/jimmunol.161.8.3822
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发表时间：
1998-10
影响因子：
4.4
通讯作者：
Sheila Ranganath;W. Ouyang;Deepta Bhattarcharya;William C. Sha;Andrew Grupe;Gary Peltz;K. M. Murphy
中科院分区：
文献类型：
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作者：
Sheila Ranganath;W. Ouyang;Deepta Bhattarcharya;William C. Sha;Andrew Grupe;Gary Peltz;K. M. Murphy
以前，我们分析了近端IL-4启动子在指导Th 2特异性活性。一个800个碱基对的近端启动子在转基因小鼠中赋予一些Th 2选择性表达。然而，相对于内源性IL-4 mRNA，该区域指导极低的报告mRNA水平，表明完整的基因活性需要额外的增强子元件。在这里，我们分析了大基因组IL-4区域的增强子活性和与转录因子的相互作用。近端IL-4启动子仅被加塔-3适度增强，但某些基因组区域显著增强加塔-3启动子反式激活。一些增强区域含有结合Th 2特异性复合物的共有加塔位点。然而，将加塔-3逆转录病毒转导到发育中的T细胞中诱导IL-5达到完全Th 2水平，但仅部分恢复IL-4产生。因此，我们认为加塔-3是允许的，但不足以完全增强IL-4，并可能通过围绕IL-13/IL-4基因位点的加塔元件起作用。
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.