Transcriptional activation of immunoglobulin alpha heavy-chain genes by translocation of the c-myc oncogene.
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.
D000818:Animals; D005786:Gene Expression Regulation; D005796:Genes; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007137:Immunoglobulin alpha-Chains / Q000235:genetics*; D008745:Methylation; D051379:Mice; D009194:Myeloma Proteins / Q000235:genetics; D009857:Oncogenes; D009876:Operon; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D007137:Immunoglobulin alpha-Chains; D009194:Myeloma Proteins