Translocation affects normal c-myc promoter usage and activates fifteen cryptic c-myc transcription starts in plasmacytoma M603.
Plasmacytoma M603 contains one normal, nontranslocated c-myc gene and one translocated c-myc gene in which c-myc exon 1 is juxtaposed with the immunoglobulin heavy chain enhancer and c-myc exons 2 and 3 are juxtaposed with C alpha. We find that steady-state c-myc RNA levels are 2-4 fold elevated in M603 relative to normal liver or spleen and that these transcripts originate predominantly if not exclusively from the translocated c-myc gene. Although both promoters on the nontranslocated c-myc gene are repressed, the proximal promoter, P1, is active on the translocated 5' c-myc region which is juxtaposed with the immunoglobulin heavy chain enhancer. The 3' portion of the translocated c-myc gene is transcribed from fifteen cryptic start sites and spliced at aberrant donor and acceptor splice sites, thereby generating a mixture of transcripts with different, abnormal 5' untranslated regions. Although the reason that translocation activates the cryptic c-myc starts in M603 is not completely understood, we show that truncation of the c-myc gene is not sufficient to activate cryptic transcription sites.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004262:DNA Restriction Enzymes; D004720:Endonucleases; D007739:L Cells / Q000032:analysis; D051379:Mice; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D010954:Plasmacytoma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000235:genetics; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D012334:RNA, Neoplasm; D004720:Endonucleases; D004262:DNA Restriction Enzymes; D015719:Single-Strand Specific DNA and RNA Endonucleases