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

THE nuclear proto-oncoprotein Myc has been implicated in the control o f cell proliferation and differentiation1-3. Myc participates in trans cription4,5 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 throug h an initiator element (Inr)6. As previously observed for the bHLH act ivator USF6, Myc was found to interact cooperatively with TFII-I at bo th Inr and upstream E-box promoter elements. However, in this case Myc interactions with TFII-I at the Inr lead to an inhibition of transcri ption 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 M yc, but only slowly. These observations indicate that Myc has the pote ntial to interact physically and functionally with components of the g eneral transcription machinery.