Transcription of c-myc in human mononuclear cells is regulated by an elongation block

Human mononuclear cells (MNC) isolated from tonsils express very low amounts of c-myc RNA. High expression of the c-myc gene is achieved by stimulation of MNC with pokeweed mitogen (PWM). Nuclear run-on transcription experiments revealed activation of the c-myc gene on the transcriptional level. In unstimulated cells a high transcriptional activity is observed on exon 1, but not on exon 2 and 3. After PWM stimulation, however, a high transcription rate is detected on the entire c-myc gene. Therefore, we conclude that c-myc gene expression in MNC is regulated by an RNA elongation block within the first exon. The analysis of the c-myc chromatin structure revealed that DNAaseI hypersensitive site II upstream of the gene is present in unstimulated as well as stimulated MNC, indicating that accessibility of this site is an essential but not sufficient requirement for c-myc gene expression.