Differential promoter utilization by the c-myc gene in mitogen- and interleukin-2-stimulated human lymphocytes.

Transcription of the c-myc gene is initiated from two principal promoters, P1 and P2. We demonstrate here that a shift in promoter utilization occurred with time in human peripheral blood mononuclear cells (PBMC) that had been stimulated to proliferate. The P1/P2 ratio reached a maximum of approximately 1.3 at 4 h after phytohemagglutinin stimulation and a minimum of 0.31 at 48 h. Actinomycin decay experiments demonstrated that both P1 and P2 transcripts had similar half-lives at early and late times after mitogen stimulation, indicating that the shift in promoter utilization was probably not posttranscriptionally regulated. Addition of interleukin-2 to previously activated PBMC increased c-myc mRNA, but unlike increases after mitogen stimulation, the P1/P2 ratio stayed less than 0.5. Our findings demonstrated that there was a difference between mitogen- and interleukin-2-stimulated increases in c-myc RNA in PBMC.