Tumor necrosis factor and gamma-interferon repress transcription from the c-myc P2 promoter by reducing E2F binding activity.

Transcription of the c-myc gene in HeLa cells has been shown to be repressed by the combined action of tumor necrosis factor (TNF) and gamma-interferon (gamma-INF). Shown here, these two cytokines inhibit proliferation of Hela cells with a coordinate inhibition of c-myc gene expression. It was found that these two cytokines exert their effects on the more proximal region of the c-myc P2 promoter. Using c-myc promoter:CAT constructs, it was found that the combined action of these cytokines significantly repress transcription from P2. This repression occurred through the E2F site within the promoter and not the ME1a2 or ME1a1 sites. However, these cytokines had no effect on transcription from the rous sarcoma virus promoter or the SV40 virus early promoter. Protein binding assays indicate that TNF and gamma-INF did not effect the ability of the ME1a2 factor to bind to its site but did significantly repress E2F factor binding to its DNA sequence.