A two-step “hand off” model for reversal of the autoinhibitory effect of TFIID. When activators are absent, TAND-1 and -2 bind to the concave and convex surface of TBP, respectively, and keep TFIID in a latent state as shown in A. Acidic activators and TAND-1 competitively bind to the concave surface of TBP, whereas TFIIA and TAND-2 competitively bind to the convex surface of TBP. Competitive binding by activation domains and TFIIA could cause a conformational alteration of TFIID that may result in formation of an intermediate state as illustrated in B. Importantly, several lines of evidence shown in this paper indicate that this intermediate stage is essential for activation of transcription. The activation domain still prevents TBP from binding to the TATA box in the intermediate stage. However, activators and TFIIA may induce conformational alteration of TFIID, allowing stabilized interaction of TFIID with sequences near and downstream from the transcriptional initiation site. Through these interactions, TBP is handed from activation domains to TATA box as shown in C.