Basal transcription factor

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. 

TFIIA and TFIIB are two basal transcription factors that are involved in the nucleation stages of the preinitiation complex by binding to the TBP-TATA box complex. Crystal structures of the ternary complex TFIIA-TBP-TATA box have been determined by the groups of Paul Sigler, Yale University, and Timothy Richmond, ETH, Zurich, and that of the TFIIB-TBP-TATA box by Stephen Burley and collaborators. The TBP-DNA interactions and the distortions of the DNA structure are essentially the same in these ternary complexes as in the binary TBP-TATA complex. 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes. Figure 1 General mechanism for transcriptional activation of CYP genes by xenochemicals that activate their cognate xeno-receptor proteins. In the case of Ah receptor, the receptor s heterodimerization partner is Arnt, whereas in the case of the nuclear receptors CAR, PXR, and PPARa, the heterodimerization partner is RXR. The coactivator and basal transcription factor complexes shown are each comprised of a large number of protein components. 

This consists of DNA-dependent RNA polymerase II and basal transcription factors (TFIIX, X = A - H). First, the basal factor TFIID binds to the promoter. TFIID, a large complex of numerous proteins, contains TATA boxbinding protein (TBP) and so-called TAFs (TBP-associated factors). The polymerase is attached to this core with the help of TFIIB. Before transcription starts, additional TFs have to bind, including TFIIH, which has heli-case activity and separates the two strands of DNA during elongation. In all, some 35 differ-... 

HRE - hormone response element TAFs - TBP-associated factors TBP - TATA box-binding protein A-H - basal transcription factors... 

Fig. 1.32. Phosphorylation of the C-terminal domain of RNA polymerase II and the beginning of transcription. The transition from the initiation complex to actual begin of transcription is regulated via phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. In the above model it is assumed that initially a complex is formed between TFIID and a holoenzyme of RNA polymerase consisting of RNA polymerase II and associated factors (mediators, SRB proteins) and the basal transcription factors. Phosphorylation of the C-terminal domain effects the dissociation of the RNA polymerase from the initation complex and the transition to the elongation phase. A protein kinase, which is part of TFIIH, is responsible for the phosphorylation. The nature of the signal that induces phosphorylation of RNA polymerase II remains unknown. SRB suppressor of RNA polymerase B. After Koleske and Young (1995).

The TAFs are components of TFIID (see table 1.1) and are required for a regulated transcription (review Verriijzer and Tijan 1996, Bmley and Roeder, 1996 ). Thus, the stimulation of transcription by the transcriptional activators Spl and NTF-1 depends upon the presence of specific TAFs in the TFllD complex. The TAFs mediate interactions between the transcriptional activators and the TFllD complex in many cases direct protein-protein interactions could be demonstrated between the activators and TAFs. Some of the TAFs possess additional enzymatic activities which allow them to participate in the regulation of transcription. By this token, the histone acetylase and protein kinase activity of TAFn250 is ascribed a regulatory function in the remodeling of chromatin and in the control of the activity of the basal transcription factors. 

Direct inhibition of the formation of a pre-initiation complex complexation of basal transcription factors, such as TFIID or TFIIB, or competition with TFIIB for binding to the promoter. An example for this type of repression is the negative cofactor NC2 (see 1.4.3.2). Transcription repression can also result from phosphorylation of the basal transcription factors. By this token, the repression of transcription observed during mitosis is attributed to the hyperphosphorylation of TBP and TAFs. 

Fig. 1.40. Model of repression and activation of transcription. The figure illustrates various mechanisms of repression of transcription, a) genes are in a generally repressed states in inactive chromatin. In a first phase of activation the chromatin is restrnctured. b) The promoter is now accessible for the binding of the basal transcription factors and for RNA polymerase II. c) An initiation complex is formed that contains the central components of the transcription apparatns, bnt which enables transcription only at a low rate, d) the binding of repressors to the transcription initiation complex can prevent fnrther activation of transcription at this step, e) the binding of transcription activators to their DNA elements leads to activation of transcription, f) an active repression is affected by proteins that bind seqnence specifically to DNA elements and in their DNA-bound form inhibit the transcritption preventing interactions with the transcription apparatus.

Reese, J.C. (2003) Basal transcription factors. Curr. Opin. 

Mediators and coactivators. Transcriptional activators that act in a crude cell-free system often do not function with purified DNA, RNA polymerase, and the basal transcription factors as indicated in Eq. 28-5. Studies with yeast, Drosophila, and human cells revealed that additional large multisubunit complexes known as mediators are needed 272/346-348 A yeast mediator complex consists of 20 subunits.349-350b Many activator proteins bind to the DNA sequences known as enchancers, discussed in the next section. Mediator complexes may also interact with enhancer-bound activators. Individual proteins, such as the TAF subunits, that bind to and cooperate with activator proteins are often called coactivators.351... 

First we discuss basal transcription factors (fig. 28.12). With all three polymerases, two or more basal transcription factors are required, and some or most of these factors must bind to the promoter before the polymerase can bind. 

The promoter region for RNA polymerase I also involves the cooperative binding of additional basal transcription factors. In this case two transcription factors bind upstream of the transcription start site (see fig. 28.12a). 

A simplified diagram of transcription is shown here. Double-stranded DNA (dsDNA) is shown as a long rectangle. RNA polymerase binds to a region of DNA called a core promoter The core promoter consists of all the DNA between the TATA sequence and the transcription start site. The core promoter is a short stretch of DNA that serves to bind and orient RNA polymerase, and the basal transcription factors. The TATA sequence, which is composed of only four nucleotides T A, T, and A), usually occurs about 25 base pairs upstream of the transcription start site. The TATA-binding protein is a special protein that binds to the TATA sequence prior to initiating transcription. 

Several families of transcription factors exist. These include basal (or general) transcription factors, activators, and repressors. The basal transcription factors include transcription factor IIA (TFUA), TFIIB, TRID, TFIIE, TRIP, and TFllH. Most of these transcription factors exist as multiprotein complexes. These transcription factors must be assembled just upstream of the transcribed part of the gene before RNA polymerase begins its catalytic activity. When assembled, the entire "mega-complex" consists of about 50 proteins (Jacobson and Tjian, 1996). 

How do the special transcription factors regulate the activities of the basal transcription factors Information on this issue is only beginning to become available. One might expect, for example, to find a scenario where RXR/VDR directly contacts TFIIA, to stimulate the activity of the initiation complex. 

Jurutka, P. W., Hsieh, j.-C., Remus, L. S., Whitfield, G. K., Thomp.son, P. D., Haussler, C., Blanco, J C, Ozato, K and Haussler, M. R, (1997). Mutations in the 1,25 dihydroxyvi-tamin II3 receptor identifying C-terminal amino acids required for transcriptional activation that are functionally dissociated from hormone binding, hetenodimeric DMA binding, and interaction with basal transcription factor IIB, in vitro. J. Biol. Chsm. 272, 14592-14599,... 

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