Modulation of a constitutive transcriptional block at exon-1 controls human c-myc oncogene expression

Abstract

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.