A direct role of transcription factor E2F in c-myc gene expression during granulocytic and macrophage-like differentiation of HL60 cells.

The transcription factor E2F is known to play an important role in cell cycle progression through interaction with retinoblastoma protein. HL60 cells are able to differentiate into a granulocytic lineage by prolonged exposure to retinoids and into a macrophage-like lineage by exposure to tumor promoter 12-O-tetradecanoylphorbol 13-acetate, with a rapid decrease of c-myc gene expression. In this study, we assessed the changes of the E2F-binding pattern to the P2 promoter region of the c-myc gene during differentiation into both lineages. The observed changes of the E2F-binding pattern were a decrease of free E2F and an appearance of retinoblastoma protein-containing E2F complexes in both lineages. The effects of the anti-c-myc antibody and the recombinant c-Myc protein on the E2F-binding patterns suggest that the c-Myc protein is not involved directly in these changes. These changes also led the suppression of transcriptional initiation from the P2 promoter. The results indicate that, in the course of HL60 cell differentiation, E2F plays a direct role in the transcriptional control of the c-myc gene through interaction with the retinoblastoma protein. A potential role for the c-Myc protein is discussed in relation to an existing state of E2F and E2F-RB complexes in the HL60 cells.