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Long-range distal elements within the Ifng locus (136.41)

2009; American Association of Immunologists; Volume: 182; Issue: 1_Supplement Linguagem: Inglês

10.4049/jimmunol.182.supp.136.41

1550-6606

Patrick L. Collins, Mel Henderson, Shojang Chang, Doug P. Mortlock, Tom Aune,

interferon and immune responses

Abstract Transgenic mice carrying an 8.6 kb Ifng transgene do not recapitulate Th1/Th2 selectivity, but mice carrying a transgene with the surrounding 190 kb of non-coding sequences do. It is unknown why Ifng requires 190 kb of regulatory sequences and space. To understand distal regulation of Ifng, we constructed transgenic mice carrying ~40 kb deletions within the 190 kb transgene. We identified two large regions which regulate Ifng expression. We then created small, 1 kb, deletions to identify specific regulatory elements. We identify two 1 kb regions at -30 kb and at -77 kb which are necessary for IFN-g transcription and repress IFN-g transcription, respectively. Our results demonstrate that multiple long-range distal regulatory elements cooperate to drive the proper temporal and quantitative expression of a single gene.