Regulation of human Ig lambda light chain gene expression by NF-kappa B.
The human Iglambda 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 Iglambda 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 kappa genes, but not the lambda genes, is dependent on constitutive NF-kappaB 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 Iglambda enhancer contain functional NF-kappaB sites that act synergistically on expression. We further show that the chicken lambda enhancer also contains a functional NF-kappaB site but the mouse lambda enhancer contains a mutated, nonfunctional NF-kappaB site that is responsible for its low enhancer activity. It is possible that the inactivating mutation in the mouse Iglambda enhancer was compensated for by an expansion of the Igkappa L chain locus, followed by a contraction of the Iglambda locus in this species.
Combriato
Gabriele
G
Adolf Butenandt Institut Molekularbiologie, Schillerstrasse 44, D-80336 Munich, Germany.
Klobeck
H Gustav
HG
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002645:Chickens; D003850:Deoxyribonuclease I / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D005803:Genes, Immunoglobulin; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017354:Point Mutation; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D007146:Immunoglobulin lambda-Chains; D016328:NF-kappa B; D003850:Deoxyribonuclease I