DIRECT ROLE FOR MYC IN TRANSCRIPTION INITIATION MEDIATED BY INTERACTIONS WITH TFII-I

THE nuclear proto-oncoprotein Myc has been implicated in the control of cell proliferation and differentiation1-3. Myc participates in transcription4,5 and belongs to the basic-helix-loop-helix (bHLH) family of regulatory proteins2,3. Here we show that Myc interacts with TFII-I, a transcription initiation factor that activates core promoters through an initiator element (Inr)6. As previously observed for the bHLH activator USF6, Myc was found to interact cooperatively with TFII-I at both Inr and upstream E-box promoter elements. However, in this case Myc interactions with TFII-I at the Inr lead to an inhibition of transcription initiation. This inhibition is selective for a TFII-I-dependent (as opposed to TFIIA-dependent) initiation pathway and correlates with the prevention of complex formation between the TATA-binding protein TBP (TFIIDtau), TFII-I and the promoter. TBP probably interacts with Myc, but only slowly. These observations indicate that Myc has the potential to interact physically and functionally with components of the general transcription machinery.