Preinitiation complex assembly

Valasek, L., Nielsen, K. H., Zhang, F., Fekete, C. A., and Hinnebusch, A. G. (2004). Interactions of Eukaryotic Translation Initiation Factor 3 (eIF3) Subunit NIPl/c with elFl and eIF5 promote preinitiation complex assembly and regulate start codon selection. Mol. Cell. Biol. 24, 9437-9455. 

Lu W, Peterson R, Dasgupta A, Scovell WM (2000) Influence of HMG-1 and adenovirus oncoprotein ElA on early stages of transcriptional preinitiation complex assembly. J Biol Chem 275 35006-35012 Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucle-osome core particle at 2.8 A resolution. Nature 389 251—260 Lusser A, Kadonaga JT (2004) Strategies for the reconstitution of chromatin. Nat Methods 1 19-26 Maeshima K, Laemmli UK (2003) A two-step scaffolding model for mitotic chromosome assembly. Dev Cell 4 467-480... 

Jiang W, Nordeen SK, Kadonaga JT (2000) Transcriptional analysis of chromatin assembled with purified ACF and dNAPl reveals that acetyl-CoA is required for preinitiation complex assembly. J.Biol.Chem 22 39819-39822... 

Tsai, E T.E. and Sigler, P. B. (2000). Structural basis of preinitiation complex assembly on human Pol 11 promoters. EMBO. 19,25-36. 

Dolezal P, Likic V, Tachezy J, Lithgow T (2006) Evolution of the molecular machines for protein import into mitochondria. Science 313 314-318 Dong J-S, Lai R, Nielsen K, Fekete CA, Qiu H-F, Hinnebusch AG (2004) The essential ATP-binding cassette protein Rlil functions in translation by promoting preinitiation complex assembly. J Biol Chem 274 42157-42168 Ellis JE, Setchell KD, Kaneshiro ES (1994) Detection of ubiquinone in parasitic and free-living protozoa, including species devoid of mitochondria. Mol Biochem Parasitol 65 213-224... 

Roeder, R. G., The complexities of eukaryotic transcription initiation Regulation of preinitiation complex assembly. Trends Biochem. Sci. 16 402-407, 1991. 

In this section, we review current understanding of how activators and repressors control chromatin structure and preinitiation complex assembly. In the next section of the chapter, we discuss how the concentrations and activities of activators and repressors themselves are controlled, so that gene expression is precisely attuned to the needs of the cell and organism. 

Multiple interactions between RNA polymerase I, TIF-1A and TAFI subunits regulate preinitiation complex assembly at the ribosomal gene promoter. EMBO Rep. 3(11), 1082-1087. 

II. Brfl-TFIIIC A Limiting Interaction in Preinitiation Complex Assembly. 95... 

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. 

Figure 7.5 Model of ferritin (and erythroid a-aminolaevulinate synthase) translation/ribosome binding regulation by IRP. In (a), with IRP not bound to the IRE (1) binding of the 43S preinitiation complex (consisting of the small ribosomal 40S subunit, GTP and Met-tRNAMet) to the mRNA is assisted by initiation factors associated with this complex, as well as additional eukaryotic initiation factors (elFs) that interact with the mRNA to facilitate 43S association. Subsequently (2), the 43S preinitiation complex moves along the 5 -UTR towards the AUG initiator codon, (3) GTP is hydrolysed, initiation factors are released and assembly of the 80S ribosome occurs. Protein synthesis from the open reading frame (ORF) can now proceed. In (b) With IRP bound to the IRE, access of the 43S preinitiation complex to the mRNA is sterically blocked. From Gray and Hentze, 1994, by permission of Oxford University Press.

These may enhance or obstruct the assembly of the preinitiation complex of RNA polymerase and relevant transcription factors [9]. Physiological isoform expression varies with cell type and maturity. In rat heart, the predominant form shifts from neonatal a3 to adult a2. 

Pauli, T.T., Carey, M., and Johnson, R.C. (1996) Yeast HMG proteins NHP6A/B potentiate promoter-specific transcriptional activation in vivo and assembly of preinitiation complexes in vitro. Genes Dev. 10, 2769-2781. 

The potential impact of the chromatin structure on ERa- and ER/1-mediated transcriptional activities was investigated using an in vitro chromatin assembly assay. These experiments have shown that the AF-1 domain of ERa, but not of ER/1, contains a transferable activation domain, which permits the ERa to efficiently activate transcription on chromatin templates [58]. Furthermore, the co-activators CBP/p300 and SRC have to be recruited to the ERa in order to maximally enhance transcription on ERa-susceptible chromatin templates. The p300/CBP-SRC complex, when interacting with the AF-1 of the ERa, is primarily involved in the stable formation of the preinitiation complex of transcription [59]. 

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... 

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. 

In previous sections many of the eukaryotic proteins and DNA sequences that participate in transcription and its control have been introduced. In this section, we focus on assembly of transcription preinitiation complexes involving RNA polymerase II (Pol II). Recall that this eukaryotic RNA polymerase catalyzes synthesis of mRNAs and a few small nuclear RNAs (snRNAs). Mechanisms that control the assembly of Pol II transcription preinitiation complexes, and hence the rate of transcription of protein-coding genes, are considered in the next section. 

Sequential Assembly of Proteins Forms the Pol II Transcription Preinitiation Complex in Vitro... 

Detailed biochemical studies revealed how the Pol II preinitiation complex, comprising a Pol II molecule and general transcription factors bound to a promoter region of DNA, is assembled. In these studies DNase I footprinting and electrophoretic mobility shift assays were used to determine the order in which Pol II and general transcription factors bound to TATA-box promoters. Because the complete, multisubunit TFIID is difficult to purify, researchers used only the isolated TBP component of this general transcription factor in these experiments. Pol II can initiate transcription in vitro in the absence of the other TFIID subunits. 

This complex in turn binds to Pol II and directly regulates assembly of transcription preinitiation complexes. 

We can now see that the assembly of a preinitiation complex and stimulation of transcription at a promoter results from the interaction of several activators with various multiprotein co-activator complexes. These Include chromatin-remodeling complexes, histone acetylase complexes, and a mediator complex. While much remains to be learned about these processes. It Is clear that the net result of these multiple molecular events Is that activation of transcription at a promoter depends on highly cooperative interactions InltT... 

---