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

Abstract

Our previous studies with the mouse myeloma MOPC 315 (IgA, λ2) cell line, using myeloma mutants that had deleted the productive α heavy (H)-chain gene, had shown that the excluded α constant-region ( Cα) allele in these cells is transcriptionally active1. 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 Cα allele2–4. The mRNA coding strand of DNA for the c-myc gene is on the opposite strand from the immunoglobulin gene in this locus2,3,5. We have now investigated the relationship between the c-myc translocation and transcriptional activity of excluded Cα alleles in IgA- and IgG-producing mouse myeloma tines. We report here that c-myc-Cα recombination events correlate with demethylation and transcription of Cα genes. Several novel Cα RNA species are produced, which are transcribed from the immunoglobulin-gene sense strand. The larger Cα RNAs appear to contain c-myc sequences. Thus the anti-sense strand of the c-myc gene provides a promoter for transcription of the Cα 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.