Transcriptional activation of immunoglobulin alpha heavy-chain genes by translocation of the c-myc oncogene

Abstract

Our previous studies with the mouse myeloma MOPC 315 (IgA, lambda 2) cell line, using myeloma mutants that had deleted the productive alpha heavy (H)-chain gene, had shown that the excluded alpha constant-region (C alpha) allele in these cells is transcriptionally active. Recent reports from several laboratories have demonstrated that in many BALB/c mouse myelomas, including MOPC 315, the DNA segment encoding the c-myc oncogene is translocated to a C alpha allele. The mRNA coding strand of DNA for the c-myc gene is on the opposite strand from the immunoglobulin gene in this locus. We have now investigated the relationship between the c-myc translocation and transcriptional activity of excluded C alpha alleles in IgA- and IgG-producing mouse myeloma lines. We report here that c-myc-C alpha recombination events correlate with demethylation and transcription of C alpha genes. Several novel C alpha RNA species are produced, which are transcribed from the immunoglobulin-gene sense strand. The larger C alpha RNAs appear to contain c-myc sequences. Thus the anti-sense strand of the c-myc gene provides a promoter for transcription of the C alpha gene. This result suggests that in other transformed cells with a c-myc-immunoglobulin gene translocation, including many Burkitt's lymphomas, activation of the adjacent immunoglobulin gene would occur.