Transcription complex

Rees WA, Keller R W, Vesenka J P, Yang G and Bustamente C 1993 Evidence of DMA bending in transcription complexes imaged by scanning force microscopy Sc/e/ ce 260 1646... 

Hori, R., Carey, M. The role of activators in assembly of RNA polymerase 11 transcription complexes. 

Activator Protein-1 (API) comprises transcriptional complexes formed by dimers of members oftheFos, Jun, and ATF family of transcription factors. These proteins contain basic leucine zipper domains that mediate DNA binding and dimerization. They regulate many aspects of cell physiology in response to environmental changes. 

An essential step of NR action is the interaction of these receptors with the specific DNA sequence HREs. Indeed, HREs position the receptors, and the transcriptional complexes recruited by them, close to the target genes. HREs are bipartite elements that are composed of two hexameric core half-site motifs. These consensus nucleotide sequences form direct, indirect, or inverted repeats, which consist of two half-sites separated... 

Figure 37-9. The eukaryotic basal transcription complex. Formation of the basal transcription complex begins when TFIID binds to the TATA box. It directs the assembly of several other components by protein-DNA and protein-protein interactions. The entire complex spans DNA from position -30 to +30 relative to the initiation site (+1, marked by bent arrow). The atomic level, x-ray-derived structures of RNA polymerase II alone and ofTBP bound to TATA promoter DNA in the presence of either TFIIB or TFIIA have all been solved at 3 A resolution. The structure of TFIID complexes have been determined by electron microscopy at 30 A resolution. Thus, the molecular structures of the transcription machinery are beginning to be elucidated. Much of this structural information is consistent with the models presented here.

Figure 37-10. Two models for assembly of the active transcription complex and for how activators and coactivators might enhance transcription. Shown here as a small oval is TBP, which contains TFIID, a large oval that contains all the components of the basal transcription complex illustrated in Figure 37-9 (ie, RNAPII andTFIIA,TFIIB, TFIIE,TFIIF, and TFIIFI). Panel A The basal transcription complex is assembled on the promoter after the TBP subunit of TFIID is bound to the TATA box. Several TAFs (coactivators) are associated with TBP. In this example, a transcription activator, CTF, is shown bound to the CAAT box, forming a loop complex by interacting with a TAF bound to TBP. Panel B The recruitment model. The transcription activator CTF binds to the CAAT box and interacts with a coactivator (TAF in this case). This allows for an interaction with the preformed TBP-basal transcription complex. TBP can now bind to the TATA box, and the assembled complex is fully active.

Work by facilitating binding of the basal transcription complex to the promoter... 

Figure 39-17. Proteins that regulate transcription have several domains. This hypothetical transcription factor has a DNA-binding domain (DBD) that is distinct from a ligand-binding domain (LBD) and several activation domains (ADs) (1-4). Other proteins may lack the DBD or LBD and all may have variable numbers of domains that contact other proteins, including co-regulators and those of the basal transcription complex (see also Chapters 42 and 43).

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

Bukrinskaya A, Brichacek B, Mann A, Stevenson M. Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton. J Exp Med 1998 188(11) 2113—2125. 

Through these examples, I wanted to illustrate the fact that the expression molecular description can have at least three different meanings. These three levels of representation are not independent. For instance, the atoms and bonds that make up the jaws of RNA polymerase II can be described, as well as RNA polymerase II can be integrated, with transcription factors and DNA, in the general picture of the preinitiation transcription complex. However, in order to answer a specific question, one particular level of description is always more significant, better adapted than others, with a greater explanatory value. 

At least seven proteins, besides the RNA-polymerase II, participate in the transcription machinery. The initiation of the transcription occurs when the transcriptional complex in the promoter region of the gene has been stabilized. The receptor dimer forms a complex of high affinity with the sequence of the HRE. This binding provides a firm base for the anchorage and stabilization of the transcriptional complex. The dimeric structure of the receptor acquires affinity to attract different coactivators that bring together the proteins of the transcriptional complex (Fig. 1.9). 

The formation of a transcriptionally active complex requires the interaction of all transcription cofactors with their respective specific DNA sequences. Once they have bound to their specific sequences, it is on these that the remaining elements of the complex that do not interact directly with the DNA are assembled (Chin 1995 Filardo 2002). The elements of the complex that do not come into direct contact with DNA have their own specificity of interaction with the remaining proteins of the complex. Therefore, they include important restrictions so that a fully active transcriptional complex can be assembled with difficulty on a receptor dimer that has incorrectly recognized a HRE. Indeed, an incorrect interaction can imply a noticeable degree of transcription inhibition. 

Raloxifene is also anchored to the same three amino acids as estradiol by direct hydrogen bonds, but it also interacts with Asp 351. The final orientation of raloxifene within the binding pocket determines that its side chain displaces helix 12. Then, helix 12 becomes reoriented and cannot seal the pocket containing the ligand (MacGregor et al. 1998). The repositioned AF-2 region impairs the formation of transcription complex by coactivators, and the signal transduction is blocked. 

TFIIIC subunits TFIIIC90 and TFIIICllO. The known function of TFIIIC is to initiate transcription complex formation by binding to promoter DNA and recruiting TBP-containing TFIIIB and RNA polymerase III, that directs synthesis of tRNA precursors. TFIIIC have an intrinsic HAT activity. 

Gene expression requires that chromatin be opened for access by transcription complexes (RNA polymerase and transcription factors, Chapter 5). Chromatin-modifyLi activities include ... 

---