A novel enhancer in the immunoglobulin lambda locus is duplicated and functionally independent of NF kappa B.
As a first step toward defining the elements necessary for lambda immunoglobulin gene regulation, DNase I hypersensitive sites were mapped in the mouse lambda locus. A hypersensitive site found 15.5 kb downstream of C lambda 4 was present in all the B-cell but not in the T-cell lines tested. This site coincided with a strong B-cell-specific transcriptional enhancer (E lambda 2-4). This novel enhancer is active in myeloma cells, regardless of the status of endogenous lambda genes, but is inactive in a T-cell line and in fibroblasts. The enhancer E lambda 2-4 functions in the absence of the transcription factor NF kappa B, which is necessary for kappa enhancer function. No evidence could be found for NF kappa B binding by this element. Rearrangement of V lambda 2 to JC lambda 3 or JC lambda genes deletes E lambda 2-4; however, a second strong enhancer was found 35 kb downstream of C lambda 1, which cannot be eliminated by lambda gene rearrangements. The second lambda enhancer (E lambda 3-1) is 90% homologous to the E lambda 2-4 sequence in the region determined to comprise the active enhancer and likewise lacks the consensus binding site for NF kappa B. The data support a model for the independent activation of kappa and lambda gene expression based on locus-specific regulation at the enhancer level.
Hagman
J
J
Department of Molecular Genetics and Cell Biology, Chicago, Illinois 60637.
Rudin
C M
CM
Haasch
D
D
Chaplin
D
D
Storb
U
U
D000818:Animals; D001402:B-Lymphocytes; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D003001:Cloning, Molecular; D003360:Cosmids; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D016328:NF-kappa B; D015183:Restriction Mapping; D013601:T-Lymphocytes; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007146:Immunoglobulin lambda-Chains; D016328:NF-kappa B; D014157:Transcription Factors; D003850:Deoxyribonuclease I