A 125 bp region of the Ig V(H)1 promoter is sufficient to confer lymphocyte-specific expression in transgenic mice

Abstract

Ig variable region (V(H)) promoters are active only in B cells and extinction experiments suggest that they are negatively regulated in non-B lineage cells. In contrast to the multiple transcription factor binding sites which occur in Ig enhancers, only a few functionally important transcription factor binding sites have been identified in V(H) promoters. In this study, we have used transgenic animals to test the functional importance of a 5' portion of the V(H)1 promoter which is known to contain a matrix attachment region as well as binding sites for the negative regulator NF-μNR and Bright, a protein complex which is induced upon stimulation of B cells with IL-5 and antigen. Our results show that none of these regions is required for V(H)1 promoter activity in the context of a rearranged μ gene. In fact, a truncated promoter extending only 125 bp upstream of the transcription initiation site was sufficient to confer strong expression in lymphocytes with negligible expression in any other tissue. These results define the smallest known region of a V(H) promoter which is capable of lymphoid-specific activity and establish the simplicity of the V(H)1 promoter element.