Activation of the immunoglobulin kappa 3' enhancer in pre-B cells correlates with the suppression of a nuclear factor binding to a sequence flanking the active core.
Both the kappa intron and the kappa 3' enhancer are required for high levels of immunoglobulin kappa gene expression. The activity of both enhancer elements can be induced by LPS in pre-B cells. While the LPS induction of the kappa intron enhancer is mediated by NF-kappa B, this factor is not responsible for activation of the 3' enhancer. Dissection of the 3' enhancer has shown that in pre-B cells the activity of the kappa 3' enhancer is repressed by a region flanking an active core element. We have now scanned this flanking region for nuclear factor binding sites and have identified sites for B-cell specific E47/E12-like proteins and two ubiquitous nuclear proteins. Furthermore, we have identified a nuclear factor in pre-B cells whose binding activity is suppressed in response to LPS. In its tissue-distribution and binding specificity this factor appears to be identical to the lymphoid specific protein LEF-1. The position of the LEF-1 binding site within the 3' enhancer and its response to LPS raise the possibility that LEF-1 may be the target for a second pathway able to mediate LPS induction of immunoglobulin kappa gene transcription.
Meyer
K B
KB
Wellcome/CRC Institute of Cancer and Developmental Biology, Cambridge, UK.
Ireland
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D008070:Lipopolysaccharides; D051821:Lymphoid Enhancer-Binding Factor 1; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA