Modulation of a constitutive transcriptional block at exon-1 controls human c-myc oncogene expression.
C-myc gene down-regulation is known to be mediated by a transcriptional block at the end of exon-1 (Bentley & Groudine, 1986; Siebenlist et al., 1988). When transcription is initiated normally, this block is expected to produce a truncated RNA, but to date, this product has escaped direct detection in somatic cells. We have been able to detect a 0.38 kb c-myc exon-1 specific RNA species by northern blot analysis. This RNA appeared not only in dimethyl sulfoxide (DMSO)-induced HL-60 cells, but also in uninduced HL-60 cells, the NALM-6, REH, RPMI-8392 and TALL-1 cell lines, and in human T-cell acute lymphocytic leukemia (T-ALL) and normal peripheral blood lymphocytes (PBL), indicating that the transcriptional block producing it is constitutive. In HL-60 cells, the 0.38 kb RNA level increased on DMSO induction while the 2.3 kb c-myc mRNA was down-regulated. Upon DMSO removal, as the 2.3 kb mRNA was made again, the 0.38 kb RNA fell to preinduction levels, Thus, modulation of this constitutive block regulates the relative amounts of c-myc message available for translation in response to specific growth stimuli. This mechanism for c-myc gene regulation may be common within the hematologic system.
Division of Pediatrics, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
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D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012313:RNA / Q000032:analysis / Q000096:biosynthesis; D016372:RNA, Antisense; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D016372:RNA, Antisense; D012313:RNA; D004121:Dimethyl Sulfoxide