Regulation of the Th2 cytokine locus by a locus control region

被引:165
作者
Lee, GR
Fields, PE
Griffin, TJ
Flavell, RA [1 ]
机构
[1] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA
[2] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA
[3] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
关键词
D O I
10.1016/S1074-7613(03)00179-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:145 / 153
页数:9
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