TATA binding protein preinitiation complex

TATA-Binding Protein The first component to bind in the assembly of a preinitiation complex at the TATA box of a typical Pol II promoter is the TATA-binding protein (TBP). The complete complex includes the basal (or general) transcription factors TFIIB, TFIIE, TFIIF, TFIIH Pol II and perhaps TFIIA (not all of the factors are shown in Fig. 28-27). This minimal preinitiation complex, however, is often insufficient for the initiation of transcription and generally does not form at all if the promoter is obscured within chromatin. Positive regulation leading to transcription is imposed by the transactivators and coactivators. 

The DNA part of each control module can be divided into three main regions, the core or basal promoter elements, the promoter proximal elements and the distal enhancer elements (Figure 9.1). The best characterized core promoter element is the TATA box, a DNA sequence that is rich in A-T base pairs and located 25 base pairs upstream of the transcription start site. The TATA box is recognized by one of the basal transcription factors, the TATA box-binding protein, TBP, which is part of a multisubunit complex called TFIID. This complex in combination with RNA polymerase 11 and other basal transcription factors such as TFIIA and TFIIB form a preinitiation complex for transcription. 

Figure 9.2 Schematic model for transcriptional activation. The TATA box-binding protein, which bends the DNA upon binding to the TATA box, binds to RNA polymerase and a number of associated proteins to form the preinitiation complex. This complex interacts with different specific transcription factors that bind to promoter proximal elements and enhancer elements.

The general transcription factor TFllD is believed to be the key link between specific transcription factors and the general preinitiation complex. However, the purification and molecular characterization of TFllD from higher eucaryotes have been hampered by its instability and heterogeneity. All preparations of TFllD contain the TATA box-binding protein in combination with a variety of different proteins called TBP-associated factors, TAFs. When the preinitiation complex has been assembled, strand separation of the DNA duplex occurs at the transcription start site, and RNA polymerase II is released from the promoter to initiate transcription. However, TFIID can remain bound to the core promoter and support rapid reinitiation of transcription by recruiting another molecule of RNA polymerase. 

DNA binding by TBP is strongly dependent on the presence of T-A base pairs in the TATA box. Bending allows remote sites on the DNA, with their bound cognate specific transcription factors, to come close together such that the proteins can interact to form the transcriptional preinitiation complex. 

In vitro interactions between HMG proteins and the basal transcription machinery have also been reported. Human HMGBl binds to the TATA-box binding protein (TBP) and interferes with the normal binding of TFIIB in the preinitiation complex [154,155], thereby inhibiting TBP function both HMGBl and TFIIB independently enhance binding of TBP to TATA-box DNA [154]. Similarly, Nhp6ap promotes the formation of a complex with TBP and TFIIA at the TATA... 

Kosa, P. E, Ghosh, G., DeDecker, B. S. and Sigler, P. B. (1997). The 2.1-A crystal structure of an archaeal preinitiation complex TATA-box-binding protein/transcription factor (II)B core/TATA-box. Proc. Nat. Acad. Sci. USA 94, 6042-6047. 

FIGURE 26-8 Common sequences in promoters recognized by eukaryotic RNA polymerase II. The TATA box is the major assembly point for the proteins of the preinitiation complexes of Pol II. The DNA is unwound at the initiator sequence (Inr), and the transcription start site is usually within or very near this sequence. In the Inr consensus sequence shown here, N represents any nucleotide Y, a pyrimidine nucleotide. Many additional sequences serve as binding sites for a wide variety of proteins that affect the activity of Pol II. These sequences are important in regulating Pol II promoters and vary greatly in type and... 

TFIID (which contains the TATA-box binding protein, TBP) binds to the TATA box. TFIIA and TFIIB then bind, followed by recruitment of RNA polymerase II and TFIIF. TFIIH and TFIIE then bind to form the preinitiation complex (PIC). Kinases phosphorylate the C-terminal domain of Pol II, leading to the open complex in which the DNA strands are separated. RNA is produced during elongation as Pol II and TFIIF leave the promoter and the other general transcription factors behind. Pol II dissociates during the termination phase, and the CTD is dephosphorylated. Pol II/TFIIF is then recycled to bind to another promoter. 

The TATA box-binding protein (TBP) is a basic transcription factor absolutely required for transcription by the three nuclear RNA polymerases (7). RNA polymerase II transcription of many protein coding genes requires direct contact of the DNA by TBP, at a sequence called the TATA box, which is located approximately 30 basepairs upstream of the transcription initiation site (2). This complex directs the assembly of the remaining basic transcription factors into a preinitiation complex (i). 

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