The endogenous immunoglobulin heavy chain enhancer can activate tandem VH promoters separated by a large distance

Abstract

The availability of a clone containing two linked immunoglobulin heavy chain variable region genes located 15.8 kb apart has allowed us to study the functional capabilities of the immunoglobulin heavy chain transcriptional enhancer element in its normal chromosomal context. In plasmacytoma J606 the 3' VH gene is joined to D and J gene segments, located within 1.7 kb of the heavy chain enhancer, and expressed; the 5' VH gene is 17.5 kb from the enhancer in J606 DNA. Run-on transcription in isolated nuclei demonstrated specific transcription of the 5' VH gene in J606 that was 60% that of the expressed 3' VH gene. No other enhancer elements are detectable closer to the 5' VH gene than the known heavy chain enhancer. Thus, the heavy chain enhancer appears to be capable of activating transcription of a VH promoter located 17.5 kb away and of activating two tandem VH promoters.