Regulation of the Th2 cytokine locus by a locus control region
Regulation of the Th2 cytokine locus by a locus control region
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DOI：
10.1016/s1074-7613(03)00179-1
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发表时间：
2003-07-01
期刊：
影响因子：
32.4
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Lee, GR;Fields, PE;Flavell, RA
Th2细胞因子基因IL - 4、IL - 5和IL - 13成簇存在，并以细胞谱系特异性的方式表达。我们利用含有携带IL - 4启动子 - 荧光素酶报告基因的鼠Th2细胞因子簇的细菌人工染色体（BAC）转基因小鼠，研究了这些基因的整体基因座特异性调控。来自这些转基因小鼠的效应CD4 T细胞中IL - 4启动子活性很强，具有Th2特异性且依赖拷贝数，这表明在该基因座中存在一个基因座控制区（LCR）。这些细胞产生IL - 4和IL - 13（而非IL - 5）也依赖拷贝数。缺失分析将RAD50基因中的一个25kb片段确定为包含LCR活性的区域。无论在基因座中的位置如何，GATA - 3都能反式激活IL - 4启动子 - 荧光素酶报告基因的表达，这表明这种调控具有整体性。然而，LCR本身并不直接对GATA - 3作出反应。
The Th2 cytokine genes IL4, IL5, and IL13 are clustered and expressed in a cell lineage-specific manner. We investigated the global locus-specific regulation of these genes using BAC transgenic mice containing the murine Th2 cytokine cluster carrying an IL4 promoter-luciferase reporter. IL4 promoter activity in effector CD4 T cells from these transgenic mice was strong, Th2 specific, and copy number dependent, suggesting the presence of an LCR in the locus. The production of IL4 and IL13, but not IL5, by these cells was also copy number dependent. Deletion analysis defined a 25 kb fragment in the RAD50 gene as the region containing the LCR activity. Expression of the IL4 promoter-luciferase reporter was transactivated by GATA-3 irrespective of position in the locus, suggesting the global nature of this regulation. The LCR itself, however, does not respond directly to GATA-3.