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Regulation of Human Ig Light Chain Gene Expression by NF-B¹

Adolf Butenandt Institut Molekularbiologie, Munich, Germany

The human Ig enhancer consists of three separated sequence elements that we identified previously by mapping DNase I-hypersensitive regions (HSS) downstream of the C region of the Ig L chain genes (HSS-1, HSS-2, and HSS-3). It has been shown by several laboratories that expression of the H chain genes as well as the genes, but not the genes, is dependent on constitutive NF-B proteins present in the nucleus. In this study we show by band-shift experiments, in vivo footprinting, and transient transfection assays that all three hypersensitive sites of the human Ig enhancer contain functional NF-B sites that act synergistically on expression. We further show that the chicken enhancer also contains a functional NF-B site but the mouse enhancer contains a mutated, nonfunctional NF-B site that is responsible for its low enhancer activity. It is possible that the inactivating mutation in the mouse Ig enhancer was compensated for by an expansion of the Ig L chain locus, followed by a contraction of the Ig locus in this species.

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