(A) PIC assembly begins with TFIID recognizing the TATA element, followed by coordinated accretion of TFIIB, the nonphosphorylated form of pol II (pol IIA) plus TFIIF, TFIIE, and TFIIH. Before elongation pol II is phosphorylated (pol IIO). Following termination, a phosphatase recycles pol II to its nonphosphorylated form, allowing the enzyme to reinitiate transcription in vitro. TBP (and TFIID) binding to the TATA box is an intrinsically slow step, yielding a long-lived protein–DNA complex. Efficient reinitiation of transcription can be achieved if recycled pol II reenters the preinitiation complex before TFIID dissociates from the core promoter. (Adapted from ref. 5.) (B) Schematic representation of functional interactions that modulate basal (Upper) and activator-dependent transcription (Lower). The basal factors TBP, TFIIB, TFIIF, TFIIE, and TFIIH and pol II are denoted by yellow symbols, with the general initiation factor contents of a “pol II holoenzyme” enclosed by square brackets. TAF_II and non-TAF_II coactivators (purple) and transcriptional activators (green) are shown interacting with their targets in the PIC. (Figure courtesy of R. G. Roeder and S. Stevens, The Rockefeller University.)

Model of the TFIIA–TFIIB–TBP–DNA complex based on the structures of the cTFIIB–TBP–TATA element (20), and the TFIIA–TBP–TATA element (21, 22) complexes (see Fig. 2A). The transcription start site is labeled with +1. The color coding scheme is the same as in Fig. 2A. (Upper) Viewed along TBP’s axis of approximate intramolecular symmetry from above the saddle. (Lower) Viewed from below the molecular saddle.

(A) Three-dimensional structures of TBP (14–16) (Upper Left), TBP complexed with the TATA element (17–19) (Upper Right), C terminal or core TFIIB (cTFIIB)–TBP–TATA element ternary complex (20) (Lower Left), and TFIIA–TBP–TATA element ternary complex (21, 22) (Lower Right). The proteins are depicted as ribbon drawings, with their N and C termini labeled when visible. The DNA is shown as a stick figure, with hypothetical, linear, B-form extensions at both ends. The transcription start site of the AdMLP is labeled with +1. TBP, and the TBP–DNA and cTFIIB–TBP–DNA complexes are shown from the same vantage point downstream of the transcription start site. The TFIIA–TBP–DNA complex is viewed from upstream of the TATA element, looking toward the transcription start site. Molecules are color coded as follows: red, cTFIIB first repeat; magenta, cTFIIB second repeat; light blue, TBP N terminus and first repeat; dark blue, TBP second repeat; green, TFIIA small subunit; yellow, TFIIA large subunit; and gray, DNA. When TBP recognizes the minor groove of the TATA element, the DNA is kinked and unwound to present the minor groove edges of the bases to the underside of the molecular saddle. On cTFIIB or TFIIA binding to the TBP-DNA complex there is essentially no change in the structure of the binary complex. (B) Structural details of TFIIB. The relative orientation of the cTFIIB’s two domains in the free and bound form is completely different. The bound and free cTFIIBs are drawn with their first domains aligned. The N and C termini of the protein fragments used in the structural studies are labeled, and the α-helices of each cTFIIB domain are colored in order red, green, blue, yellow, and magenta. A helix present only in the second domain of cTFIIB in the ternary complex is colored light blue. Structure of cTFIIB in the cTFIIB–TBP–TATA element ternary complex (20) (Left). Structure of free cTFIIB (23) (Center). Structure of the N-terminal, Zn²⁺ binding region of TFIIB (24) (Right). The Zn atom is colored in red. The 60 residues between the C terminus of the Zn²⁺ binding domain and the N terminus of cTFIIB are flexible and have not been visualized in high-resolution structural studies.

Structural similarities between transcription factors and histone proteins. (Upper) Heterotetrameric assembly of the N-terminal portions of two Drosophila TAF_IIs (dTAF_II42/dTAF_II62)₂ (60), and the corresponding view of the histone H3/H4 heterotetramer derived from the structure of the histone octamer (61) (the additional N-terminal helix of H3 visualized in this study has been omitted for clarity). (Lower) The DNA binding domain of hepatocyte nuclear factor-3γ (62), and the corresponding view of the globular domain of the linker histone H5 (GH5) (63).