Transcription initiation complex

TBP binds to the TATA box in the minor groove of DNA (most transcription factors bind in the major groove) and causes an approximately 100-degree bend or kink of the DNA helix. This bending is thought to facilitate the interaction of TBP-associated factors with other components of the transcription initiation complex and possibly with factors bound to upstream elements. Although defined as a component of class II gene promoters, TBP, by virtue of its association with... 

Beato M, Sanchez-Pacheco A (1996) Interaction of steroid hormone receptors with the transcription initiation complex. Endocr Rev 1 587... 

The mechanism by which transcription factors increase (or decrease) the rate of transcription is unclear. It is likely that, bound to the enhancer or promoter DNA sequences, they interact with other proteins to stimulate on inhibit formation of the transcription-initiator complex. 

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.

Fig. 4.4. The principle of signal transduction by nuclear receptors. Nuclear receptors are ligand-controlled transcription factors that bind cognate DNA sequences, or hormone responsive elements (HRE). The hormone acts as a regulating ligand. Most nuclear receptors bind their cognate HREs, which tend to be symmetrically organized, as homo- or heterodimers. The DNA-bound, activated receptor stimulates transcription initiation via direct or indirect protein-protein interactions with the transcription initiation complex. The arrows demonstrate the different possible configurations of the HRE (see also 4.6). H hormone Hsp heat shock protein.

Structure of chromatin which promotes transcription. A large protein complex takes part in this remodeling. Some of the proteins in the complex, like the CBP/p300 protein (see also 1.4.6), possess histone acetylase activity. The activated, DNA-boimd receptor possibly recruits a histone acetylase to the chromatin. It can thus create the conditions necessary for the formation of a transcription initiation complex by this histone modification. 

DNA bending can cause an enhancer element that is far from the promoter in the linear DNA molecule, to interact with the transcription-initiation complex. 

NtrC-P dimerizes and binds to the enhancer sequence, where it appears to catalyze an ATP-depen-dent isomerization of the closed to open forms of the transcription initiation complex (Eq. 28-1).153/154 The isomerization may depend upon looping.152 Other operons that utilize the oN subunit of RNAP often also have upstream or downstream enhancers.155156... 

Those protein-coding genes that have an initiator element instead of a TATA box (see above) appear to need another protein(s) that binds to the initiator element and facilitates the binding of TBP. The other transcription factors then bind to form the transcription initiation complex in a similar manner to that described above for genes possessing a TATA box promoter. 

Many genes are active in all cells but some are transcribed only in specific cell types, at specific times and/or only in response to specific external stimuli. Transcriptional regulation occurs via transcription factors that bind to short control elements associated with the target genes and then interact with each other and with the transcription initiation complex to increase or decrease the rate of transcription of the target gene. 

Fig. 1. Control regions that regulate transcription of a typical eukaryotic protein-coding gene. Although shown as distinct entities here for clarity, in vivo the different regulatory proteins bound to the control elements and distant enhancers interact with each other and with the general transcription factors of the transcription initiation complex to modulate the rate of transcriptional initiation.

Typically each protein-coding gene in a eukaryotic cell has several control elements in its promoter (Fig. 1) and hence is under the control of several transcription factors which interact with each other and with the transcription initiation complex by protein protein interaction to determine the rate of transcription of that gene. 

Fig. 2. Looping out of DNA allowing the interaction of enhancer-bound factors) with the transcription initiation complex.

Eukaryotic cells contain multiple copies of the 5S rRNA gene. Unlike other eukaryotic rRNA genes, the 5S rRNA genes are transcribed by RNA Pol III. Two control elements, an A box and a C box, lie downstream of the transcriptional start site. The C box binds TFIIIA which then recruits TFIIIC. TFIIIB now binds and interacts with RNA Pol III to form the transcription initiation complex. Transcription produces a mature 5S rRNA that requires no processing. 

The rRNA promoter consists of a core element which straddles the transcriptional start site (designated as position +1) from residues -31 to +6 plus an upstream control element (UCE) about 50-80 bp in size and located about 100 bp upstream from the start site (i.e. at position -100 Fig. 4b). A transcription factor called upstream binding factor (UBF) binds both to the UCE as well as to a region next to and overlapping with the core element. Interestingly, TATA box binding protein (TBP see Topic G6), also binds to the rRNA promoter (in fact, TBP is required for initiation by all three eukaryotic RNA polymerases). The UBF and TBP transcription factors interact with each other and with RNA Pol I to form a transcription initiation complex. The RNA Pol I then transcribes... 

Barton NJ, McQueen DS, Thomson D, Gauldie SD, Wilson AW, Salter DM, Chessell IP (2006) Attenuation of experimental arthritis in TRPVIR knockout mice. Exp Mol Pathol 81 166-170 Basbaum AI, Fields HL (1984) Endogenous pain control systems brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7 309-338 Beato M, Sanchez-Pacheco A (1996) Interaction of steroid hormone receptors with the transcription initiation complex. Endocr Rev 17 587-609... 

The entire top side of TBP bound to the TATA-box DNA is out of the way and is fi e to interact with other factors. This leaves a generous surface on TBP available for interactions with the multitude of factors which are parts of the transcription initiation complex. The same is true for the TFIIA/TFIIB-TBP-complexes. The extensive surfaces displayed by the TFIIA/TFIIB-TBP-DNA complexes represent potential sites for binding basal initiation factors, signal-responsive transcriptional activators, co-activators and mediators, and, most importantly, leave room for Pol II. 

The core promoter module can be defined functionally by its capability to assemble the transcription initiation complex (see Figure 4.3) and orient it specifically towards the TSS of the promoter [13], defining the exact location of the TSS. Various combinations of about four distinguishable core promoter elements that constitute a general core promoter can achieve this. This module includes the TATA box, the initiator region (INR), an upstream activating element, and a downstream element. (The TATA box is a basic... 

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