Ectopic expression of myc or myn down-regulates immunoglobulin transcription.

Co-transfection of expression vectors for c-myc or myn down-regulated the expression from a reporter plasmid containing the chloramphenicol-acetyl-transferase (CAT) gene, under the control of an immunoglobulin kappa promoter and the immunoglobulin heavy-chain enhancer. The effect was dose-dependent and an additive effect was seen when both expression vectors were transfected simultaneously. Deletion mutants lacking the leucine zipper region of c-myc were unable to down-regulate the transcription from the reporter construct. Reporter genes where the immunoglobulin enhancer had been exchanged with a SV40 enhancer or an immunoglobulin minimal enhancer were still down-regulated by a cotransfection with c-myc expression vectors. A minimal promoter containing an octamer motif responded to myc expression while a minimal promoter containing a SP1 motif did not. No direct interactions between myc, myn and Oct proteins could be detected either by band-shift analysis, or by co-translation in vitro followed by precipitation with SP6 kappa promoter bound to magnetic carriers. Furthermore, B cells from mice transgenic for myc showed aberrant expression of transcription factors.