The human lambda immunoglobulin enhancer is controlled by both positive elements and developmentally regulated negative elements.
We have recently reported the localization of the first transcriptional enhancer in the human lambda (lambda) immunoglobulin light chain locus. Enhancer activity was contained on a 1.2 kb SstI fragment, with partial activity retained on a core 111 bp PstI-SstI fragment. This enhancer is located 11.7 kb downstream of C lambda 7, the most 3' lambda constant region gene. Using a chloramphenicol acetyl transferase (CAT) assay system, we have now determined the boundaries of the complete enhancer and find it is two- to four-fold as active as the core fragment in both pre-B and B cell lines. Interestingly, a larger fragment, containing the complete enhancer as well as 5' and 3' flanking sequences has four- to eight-fold reduced activity when tested in pre-B cell lines, but full activity in B cell lines. This suggests the presence of developmentally regulated negative elements flanking the human lambda enhancer which prevent or reduce its activity at a developmentally incorrect time. By using in vivo footprinting we have begun to examine the protein interactions within this enhancer in a more physiologically relevant manner and have identified motifs which are shared with the murine lambda enhancers, as well as motifs unique to the human lambda enhancer.
Glozak
M A
MA
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101, USA.
Blomberg
B B
BB
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data
D007146:Immunoglobulin lambda-Chains