Regulation of the relative abundances of c-myc mRNAs in human promyelocytic HL60 cells

Abstract

Abstract Transcription of the c-myc gene is initiated mainly from two promoters, P1 and P2. By S1 nuclease analysis we found that there is 8 times more P2- than P1-initiated RNA in total RNA from HL60 cells. The half-lives of P1- and P2-initiated transcripts are 26 and 18 min, respectively, so the difference in the relative abundance of the mRNAs is not due to differences in their stabilities. The relative rates of transcription from the P1 and P2 promoters, estimated by in vitro nuclear run-on analysis, were found to differ by about 10-fold, sufficient to account for the difference in the steady-state levels of the two mRNAs. The abundance of c-myc mRNA changes dramatically during differentiation of HL60 cells. Dimethyl sulphoxide causes a very rapid reduction in total c-myc mRNA, while with phorbol ester a transient increase occurs followed by a more gradual decline. At no time during these dramatic alterations were significant changes detected in the relative abundance of P1- and P2-initiated mRNAs, or in their stabilities.