FUNCTIONAL-CHARACTERIZATION OF THE DEVELOPMENTALLY CONTROLLED IMMUNOGLOBULIN KAPPA 3' ENHANCER - REGULATION BY ID, A REPRESSOR OF HELIX-LOOP-HELIX TRANSCRIPTION FACTORS

We have functionally characterized an enhancer element (kappa-E3') which lies 8.5 kb downstream of the immunoglobulin kappa gene. The activity of this enhancer is developmentally controlled. It is inactive at the pre-B-cell stage but active at the B-cell and plasma cell stages. This enhancer is also functional in S107 plasmacytoma cells, which lack NF-kappa-B and therefore intron enhancer activity. The activity of the kappa-E3' enhancer therefore provides an explanation for the transcriptional activity of endogenous kappa genes in S107 cells in the absence of intron enhancer function. We have identified a 132-bp segment of the kappa-E3' enhancer that retains 75% of the activity of the entire enhancer observed in plasmacytoma cells. Within this 132-bp core, there are at least two functional elements, one of which binds to a B-cell-specific nuclear factor. This element contains a potential binding site for the B-cell- and macrophage-specific transcription factor PU.1. The kappa intron and kappa-E3' enhancers were also found to be regulatable by Id, an inhibitor of helix-loop-helix transcription factors. The site of action of Id on the kappa-E3' enhancer was mapped to a 25-bp region which contains a potential binding site for a helix-loop-helix transcription factor. A possible model for the developmental control of kappa gene transcription is discussed.