Schematic depiction of the transcription PIC. PIC assembly is nucleated by TBP binding to the TATA box, inducing a sharp bend in the DNA template, followed by association of TFIIB, RNA pol II/TFIIF, TFIIE, and TFIIH. Each pattern denotes a distinct general transcription factor. Subunit composition is indicated, except for TFIIH (9 subunits) and RNA pol II (12 subunits). Although PIC assembly can occur by stepwise addition of the general transcription factors (GTFs) in vitro, the discovery of RNA pol II holoenzyme complexes that include GTFs suggests that stepwise assembly might not occur in vivo.

Tertiary structure of a TATA-TBP-TFIIA-TFIIB complex. The amino- and carboxy-terminal direct repeats of TBP are light and dark blue, respectively. The amino- and carboxy-terminal repeats of core-TFIIB are red and orange, respectively. The Toa1 and Toa2 subunits of TFIIA are green and yellow, respectively. Reprinted from reference 351 with permission of the publisher.

Tertiary structure of TBP-2 from Arabidopsis thaliana. The three-dimensional structure is viewed perpendicular to the intramolecular twofold symmetry axis. The α-helices (H1, H2 and H1′, H2′) and β-sheets (S1 to S5 and S1′ to S5′) are labeled and can be correlated with the TBP amino acid replacement data summarized in Table 2. Reprinted from reference 342 with permission of the publisher.

Schematic summary of yeast coactivators and their activities. Transcriptional activation by a UAS-activator complex can occur by direct interaction between an acidic activator protein and components of the core transcriptional machinery or can be indirect, mediated by coactivators that interact either with components of the core transcriptional machinery (TFIIA, TAFs, SRB/mediator) or with nucleosomes (SWI/SNF, HATs). TFIIA interacts with the core transcriptional machinery through TBP, functioning as either an antirepressor or coactivator. TAFs also interact with TBP as components of the TFIID complex. Although initially thought to be requisite coactivators of transcription, TAFs now appear to be required for activation of only a subset of genes with noncanonical TATA elements. SRB/mediator is a component of an RNA pol II holoenzyme complex, interacting with RNA pol II through the CTD of Rpb1. The SRB/mediator includes subunits that function in transcriptional repression as well as activation. Several HATs have been identified in yeast, including the Gcn5-containing SAGA complex. HATs appear to mediate transcriptional activation by acetylation of nucleosomal histones, resulting in chromatin remodeling. The SWI/SNF complex also appears to facilitate chromatin remodeling, in this case by promoting nucleosome displacement in an ATP-dependent manner.

Schematic summary of general transcriptional repressors and their activities. Comparable to coactivators, general repressors can interact either with the core transcriptional machinery or with nucleosomes. Mot1, Dr1-DRAP1 (NC2), and the Ccr4-Not complex confer transcriptional repression by interaction with components of the core machinery. Mot1 interacts directly with TBP and promotes TATA-TBP dissociation in an ATP-dependent manner. Dr1-DRAP1 also interacts directly with TBP but, in contrast to Mot1, represses transcription by blocking TBP interaction with TFIIA and TFIIB rather than by displacing TBP from DNA. The Ccr4-NOT complex also targets the core machinery. Whereas Mot1 promotes TBP-DNA dissociation, the Ccr4/NOT complex has been proposed to negatively regulate the activity of factors (e.g., TFIIA) that facilitate TBP-TATA association. In contradistinction to HATs (Fig. 4), HDA complexes repress transcription by deacetylation of histones or other factors, presumably allowing reestablishment of repressive chromatin structures. HDAs do not bind DNA directly but are targeted by URS-repressor complexes. Ssn6-Tup1 is also targeted by URS-repressor complexes and was recently reported to interact with histones H3 and H4. Thus, HDAs and Ssn6/Tup1 are similar in their modes of transcriptional repression, although Ssn6/Tup1 is not an HDA. The BUR proteins, including Bur1, Bur2, Bur4, and Bur5, appear to mediate repression by affecting chromatin structure. (BUR5 is identical to HHT1/SIN2, which encodes histone H3.) The Spt4-Spt5 complex also regulates transcription by affecting the chromatin structure. Recently, a human Spt4-Spt5 complex, denoted DSIF, was identified as a transcription elongation factor. Spt6 is functionally related to Spt4 and Spt5 but does not appear to be a component of the Spt4-Spt5 complex. An important characteristic of several general transcriptional repressors is that they can also function in transcriptional activation.