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.