Transcription complex, eukaryotic

Zawel, L. and Reinberg, D. (1995) Common themes in assembly and function of eukaryotic transcription complexes. Annu. Rev. Biochem., 64, 533-561. 

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.

Depletion of histone HI after covalent modification from chromatin is a key step in eukaryotic transcription (Lee et al, 1993 Juan et al, 1994 Rice and Allis, 2001). A comparison of the association of the antibiotic Mg + complexes with the normal and HI depleted chromatin suggests that smaller ligands, like anticancer drugs, have better accessibility for HI depleted chromatin compared to native chromatin. HI depleted chromatin is also more prone to aggregation upon association with the complex I of the antibiotic Mg + complexes. It is also less accessible to micrococcal nuclease. We propose that HI depleted chromatin is a better target of these antibiotics compared to native chromatin. This observation is particularly significant in case of neoplastic cells where most of the cell nuclei are transcriptionally active, and, therefore, contain HI depleted chromatin. 

C. Eukaryotic transcription is more complex than in prokaryotes, mainly in terms of the nature of the RNA polymerases, the assembly of the pre-initiation complex, and the need for processing eukaryotic RNAs. 

Diverse Functions of TFIIH In eukaryotes, the repair of damaged DNA (see Table 25-5) is more efficient within genes that are actively being transcribed than for other damaged DNA, and the template strand is repaired somewhat more efficiently than the nontemplate strand. These remarkable observations are explained by the alternative roles of the TFIIH subunits. Not only does TFIIH participate in the formation of the closed complex during assembly of a transcription complex (as described above), but some of its subunits are also essential components of the separate nucleotide-excision repair complex (see Fig. 25-24). 

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

Allele-specific differences between regulatory polymorphisms associated with the ability of RNA polymerase II to bind and assemble its transcription complex at the start site of transcription for several eukaryotic promoters has also been measured using MALDI-TOF MS coupled with primer extension (42). This technique provides a powerful tool for identifying important regulatory SNPs and haplotypes in vivo. 

RNA synthesis, or transcription, is the process of transcribing DNA nucleotide sequence information into RNA sequence information. RNA synthesis is catalyzed by a large enzyme called RNA polymerase. The basic biochemistry of RNA synthesis is common to prokaryotes and eukaryotes, although its regulation is more complex in eukaryotes. The close connection between prokaryotic and eukaryotic transcription has been beautifully illustrated by the recently determined three-dimensional structures of representative RNA polymerases from prokaryotes and eukaryotes (Figure 28.1). Despite substantial differences in size and number of polypeptide subunits, the overall structures of these enzymes are quite similar, revealing a common evolutionary origin. 

We turn now to transcription in eukaryotes, a much more complex process than in prokaryotes. In eukaryotes, transcription and translation take place in different cellular compartments transcription takes place in the membrane-bounded nucleus, whereas translation takes place outside the nucleus in the cytoplasm. In prokaryotes, the two processes are closely coupled (Figure 28.15). Indeed, the translation of bacterial mRNA begins while the transcript is still being... 

We have seen how interactions between DNA-binding proteins such as CAP and RNA polymerase can activate transcription in prokaryotic cells (Section 31.1.6). Such protein-protein interactions play a dominant role in eukaryotic gene regulation. In contrast with those of prokaryotic transcription, few eukaryotic transcription factors have any effect on transcription on their own. Instead, each factor recruits other proteins to build up large complexes that interact with the transcriptional machinery to activate or repress Panscription. 

J.A. Goodrich and R. Tjian. 1994. TBP-TAF complexes Selectivity factors for eukaryotic transcription Curr. Opin. Cell. Biol. 6 403-409. (PubMed)... 

H. Tang, X. Sun, D. Reinberg and R.H. Ebright. Protein-protein interactions in eukaryotic transcription initiation structure of the preinitiation complex. Proc. Natl. Acad. Sci. USA 93 (1996) 1119-24. 

Pugh, B. E, and Tjian, R. (1992). Diverse transcriptional functions of the multisubunit eukaryotic TFIID complex. J. Biol. Chem. 267, 679-682. 

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