Regulation of the Th2 cytokine locus by a locus control region.
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.
Lee
Gap Ryol
GR
Section of Immunobiology, Yale University School of Medicine, Yale University, New Haven, CT 06520, USA.
Fields
Patrick E
PE
Griffin
Thomas J
TJ
Flavell
Richard A
RA
D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D050990:GATA3 Transcription Factor; D018628:Gene Dosage; D018793:Interleukin-13 / Q000235:genetics*; D019409:Interleukin-15 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D019901:Locus Control Region / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D019409:Interleukin-15; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D015847:Interleukin-4