Prokaryotes transcription factors

Zheng, M. and G. Storz. Redox sensing by prokaryotic transcription factors. Biochem. Pharmacol. 59 1-6, 1999. 

In prokaryotes, most transcription factors belong to the Helix-Turn-Helix family (19). Proteins of this class typically form homodimers, whose tridimensional structure is symmetrical. As a consequence, many prokaryote transcription factors bind to spaced motifs (also called dyads), where each halfmotif is bound by one element of the homodimer. The width of the spacing between the two contact points is transcription factor-specific, and can vary from 0 to 20 nt. Because we are working with bacterial sequences, we will illustrate the pattern discovery step by using a tool dedicated to the detection of spaced motifs dyad-analysis (20) (see Note 9). 

Fig. 3. Protein-DNA interface areas. The sample of protein-double-stranded DNA complexes analyzed by Nadassy et al. (1999) comprises 65 complexes, 16 with enzymes, 9 with prokaryotic transcription factors (TF), 37 with eukaryotic transcription factors, and 3 with miscellaneous proteins. (Top) Histogram of the interface areas. (Bottom) When the proteins are homodimers or direct repeats (of zinc fingers, for instance), which is the case for most proteins in this sample, the complexes contain two or more binding units corresponding to a monomer. The histogram is drawn for these bindings units. The five DNA complexes with zinc fingers and four with TBP are set apart from other eukaryotic transcription factors.

Tab. 13.1 Transcription factors under the control of RNI. Selected examples for the regulatory impact of RNI on prokaryotic and eukaryotic transcription factors. In a very simplistic way activation versus inhibition by RNI are indicated.

The nomenclature for transcription factors is confusing. Depending on their mode of action, various terms are in use both for the proteins themselves and for the DNA sequences to which they bind. If a factor blocks transcription, it is referred to as a repressor otherwise, it is called an inducer. DNA sequences to which regulatory proteins bind are referred to as control elements. In prokaryotes, control elements that serve as binding sites for RNA polymerases are called promoters, whereas repressor-binding sequences are usually called operators. Control elements that bind activating factors are termed enhancers, while elements that bind inhibiting factors are known as silencers. 

General transcription factors (GTFs) that bind to eukaryotic promoters are functionally analogous to a factor in prokaryotes. 

In prokaryotes and eukaryotes, the expression of individual genes is controlled by activation or inhibition of RNA polymerase on each gene by transcription factors. 

C. Eukaryotic gene regulation is much more complex than in prokaryotes, with expression dependent on several types of transcription factors as well as chromatin structure. 

The sequences of eukaryotic promoters are more variable than their prokaryotic counterparts (see Fig. 26-8). The three eukaryotic RNA polymerases usually require an array of general transcription factors in order to bind to a promoter. Yet, as with prokaryotic gene expression, the basal level of transcription is determined by the effect of promoter sequences on the function of RNA polymerase and its associated transcription factors. 

In eukaryotes, the tRNA genes exist as multiple copies and are transcribed by RNA polymerase III (RNA Pol III). As in prokaryotes, several tRNAs may be transcribed together to yield a single pre-tRNA molecule that is then processed to release the mature tRNAs. The promoters of eukaryotic tRNA genes are unusual in that the transcriptional control elements are located downstream (i.e. on the 3 side) of the transcriptional start site (at position +1). In fact they lie within the gene itself. Two such elements have been identified, called the A box and B box (Fig. 3). Transcription of the tRNA genes by RNA Pol III requires transcription factor IIIC (TFIIIC) as well as TFIIIB. THIIC binds to the A and B boxes whilst TFIIIB binds upstream of the A box. TFIIIB contains three subunits, one of which is TBP (TATA binding protein), the polypeptide required by all three eukaryotic RNA polymerases. 

RNA polymerase II transcribes messenger RNA and a few other small cellular RNAs. Class II promoters are usually defined by their sensitivity to a-amanitin. Like prokaryotic promoters, many class II promoters contain two conserved sequences, called the CAAT and TATA boxes. The TATA box is bound by a specialized transcription factor called TBP (for TATA-Binding-Factor). Binding of TBP is required for transcription, but other proteins are required to bind to the upstream (and potentially downstream) sequences that are specific to each gene. Like prokaryotic transcripts, eukaryotic RNAs are initiated with a nucleoside triphosphate. Termination of eukaryotic mRNA transcription is less well understood than is termination of prokaryotic transcription, because the 3 ends of eukaryotic mRNAs are derived by processing. See Figure 12-9. 

Two common DNA-binding structures are found in a variety of transcriptional control proteins. The helix-tum-helix motif allows interaction with DNA sequences. The two a-helices are positioned at an angle to each other. One a-helix (the binding helix) contacts the major groove of the DNA molecule. The other a-helix positions the binding helix relative to the DNA. Transcriptional control proteins can have other domains that allow their interaction with other transcription factors these protein-protein interactions allow multiple binding events to occur. Helix-tum-helix proteins are found in both prokaryotic and eukaryotic systems. See Figure 12-17. 

Zinc-fingers are common in DNA-binding proteins of eukaryotes but are not found in prokaryotes. Examples of zinc-finger proteins include the RNA polymerase III transcription factor TFIIIA, steroid receptors, and some gene products that control development. The zinc-finger consists of pairs of cysteine and/or histidine residues within an a-helix. These residues bind tightly to a Zn2+ ion, which allows the a-helical amino acids to interact with specific sequences. See Figure 12-18. 

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