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Significance Immunoglobulin isotype switching plays an important role in adaptive immune responses. It requires transcription of switch regions from inducible promoters controlled by a long-range superenhancer (3′RR). Most stimuli induce more than one promoter on both chromosomes. Thus, it is unknown whether isotype (I) promoters compete for the 3′RR on the same chromosome. By performing allele-specific RT-qPCR assays, we show that the 3′RR activates promoters by either co-activation or competition and that the nature of the inducing signal plays a pivotal role in determining the activation mode. The two activation paths may have evolved to cope with different kinetics of primary immune responses.

Two modes ofcis-activation of switch transcription by theIgHsuperenhancer