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Cutting Edge: IFN-γ Regulated Germline Transcripts Are Expressed from γ2a Transgenes Independently of the Heavy Chain 3′ Enhancers

Several results indicate that transcriptional enhancers lying 3′ of the Cα 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 γ2α gene, including promoter, I, S, and C regions. RNA was expressed from these γ2a transgenes with correct IFN-γ 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 γ2a 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 μ enhancer increased transcription from the γ2a transgene by ∼75-fold in B cells. However, this increased transcription was not responsive to IFN-γ treatment of the transgenic B cells.