Figure 3.

Upon MYC amplification in cancer, Myc recruits additional transcriptional cofactors to drive transcription: (A) BRD4 binds to acetylated lysines on histone tails and recruits P-TEFb (which includes CDK9), that phosphorylates the carboxy terminal domain of RNA Pol II. Myc can also individually recruit P-TEFb. (B) Treatment with bromodomain and extra-terminal motif (BET)/BRD4 inhibitors prevents BRD4 from binding to histone tails and treatment with CDK9 inhibitors disrupts CDK9′s kinase activity. Thus, both result in failure of activating transcription of MYC or Myc target genes.