The mechanism of inactivation of the normal c-myc gene locus in human Burkitt lymphoma cells.
In human Burkitt lymphoma, the expression of the c-myc allele that has been translocated to the immunoglobulin gene locus is constitutively elevated, whereas transcription from the normal untranslocated allele on chromosome 8 is usually undetectable. Our experiments were carried out to check several plausible mechanisms proposed to explain this selective inactivation. By examining the c-myc transcripts in the presence of cycloheximide and/or actinomycin D and using differential S1 mapping, which distinguishes the c-myc transcripts of the translocated from the untranslocated allele, we found that the selective inactivation of the normal c-myc gene locus is not by a post-transcriptional regulatory mechanism, by autorepression from the constitutive expression of c-myc protein derived from the translocated locus, nor by suppression due to the previously proposed labile protein repressor. Our results are accommodated most easily by an inactivation mechanism that stably modifies the structure of the untranslocated c-myc gene.
D002051:Burkitt Lymphoma / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005803:Genes, Immunoglobulin; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007148:Immunoglobulin mu-Chains; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003609:Dactinomycin; D003513:Cycloheximide