A 125 bp region of the Ig VH1 promoter is sufficient to confer lymphocyte-specific expression in transgenic mice.
Ig variable region (VH) 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 VH promoters. In this study, we have used transgenic animals to test the functional importance of a 5' portion of the VH1 promoter which is known to contain a matrix attachment region as well as binding sites for the negative regulator NF-microNR 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 VH1 promoter activity in the context of a rearranged micro 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 VH promoter which is capable of lymphoid-specific activity and establish the simplicity of the VH1 promoter element.
Avitahl
N
N
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Calame
K
K
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D004274:DNA, Recombinant / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005260:Female; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D019076:Transgenes
D004274:DNA, Recombinant; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains