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Cutting edge: IFN-gamma regulated germline transcripts are expressed from gamma2a transgenes independently of the heavy chain 3' enhancers.

Several results indicate that transcriptional enhancers lying 3' of the Calpha gene regulate RNA expression and switch recombination of heavy chain genes. To investigate this regulation we prepared transgenic mice with a 10.5-kb transgene that included the germline form of the murine gamma2alpha gene, including promoter, I, S, and C regions. RNA was expressed from these gamma2a transgenes with correct IFN-gamma regulation, in spite of the fact that they lacked the 3' enhancers. This RNA expression was independent of insertion site and dependent on copy number, indicating that the gamma2a gene includes locus control region-like elements. Addition of either a cassette containing 3' enhancer DNase I hypersensitive sites 1, 2, 3B, and 4 or the intronic micro enhancer increased transcription from the gamma2a transgene by approximately 75-fold in B cells. However, this increased transcription was not responsive to IFN-gamma treatment of the transgenic B cells.