The importance of the 3′-enhancer region in immunoglobulinxgene expression

Open Access
Publisher Website
Google Scholar
Abstract
The first enhancers to be identified In the immunoglobulin gene loci are located In the J-C Intron. However, deletion of the immunoglobulin x intronenhancer has little effect on the transcription of x transgenes. Here we ask whether the second x enhancer which we recently identified at the 3′-end of the locus plays a role in x gene expression. We show that its omission leads to 20–40 fold lower expression of x transgenes and to poor allelic exclusion. Transfection experiments show that activity of the 3′-enhancer, like that of the x-intron enhancer, can be induced in a pre-B cell line by incubation with bacterial lipopolysaccharide. Whereas induction of the x-intron enhancer is due to induction of NF-xB actMty, deletion mapping of the 3′-enhancer localises its activity to a 50 nucleotide region that lacks an NF-xB. site; indeed the 3′-enhancer allows x expression in a cell line which lacks NF-xB. Thus, both the 3′- and intron-enhancers can be induced at the same stage of differentiation but by distinct pathways. Furthermore, unlike the intron enhancer, the 3′-enhancer plays a critical role in the transcription of rearranged immunoglobulin x genes.