AN ALTERNATIVE PATHWAY FOR TRANSCRIPTION INITIATION INVOLVING TFII-I

THE minimal promoter elements required for initiation by RNA polymerase II include the TATA box and/or an initiator element (Inr) at or near the transcription start site1-4. Studies of the adeno-virus major late core promoter (containing both elements) have demonstrated an initiation pathway that involves binding of the transcription factor TFIID (or the derived subunit, the TATA-binding protein TBP (TFIIDtau)) to the TATA element, which is facilitated by transcription factor TFIIA, followed by sequential interactions of other general factors4-8. Here we describe a novel pathway that requires an intact Inr and the Inr-binding factor TFII-I (ref. 3). Sequential addition of the general factors generated TFII-I-dependent preinitiation complexes different from those formed with TFIIA. Furthermore, TBP bound cooperatively (with only TFII-I) to an Inr-containing TATA-less promoter, suggesting a means for activation of TATA-less promoters, which nonetheless require TFIID (refs 9-11). These observations provide support for functionally distinct pathways which could be subject to differential regulation by specific activators or repressors.