MYC and Transcription Elongation

Most transcription factors specify the subset of genes that will be actively transcribed in the cell by stimulating transcription initiation at these genes, but MYC has a fundamentally different role. MYC binds E-box sites in the promoters of active genes and stimulates recruitment of the elongation factor P-TEFb and thus transcription elongation. Consequently, rather than specifying the set of genes that will be transcribed in any particular cell, MYC's predominant role is to increase the production of transcripts from active genes. This increase in the transcriptional output of the cell's existing gene expression program, called transcriptional amplification, has a profound effect on proliferation and other behaviors of a broad range of cells. Transcriptional amplification may reduce rate-limiting constraints for tumor cell proliferation and explain MYC's broad oncogenic activity among diverse tissues.