Eukaryotic Transcriptional Control

Ghromatin modifications are important in eukaryotic transcription control. 

The end products of gene expression are proteins, mainly enzymes, and it is essential that their levels be strictly controlled. There are many potential sites of control in both bacteria and eukaryotes. DNA or gene amplification (Chap. 16) in eukaryotes is one way of responding to the demand for more of the protein product if there arc more copies of the gene, then transcription can occur at a faster rate. More often, control is effected at the level of cither transcription or translation, with the former probably being more important for both bacteria and eukaryotes. Transcriptional control in bacteria is particularly effective because of the very short half-life (a few minutes) of mRNA in such cells the half-life is longer in eukaryotes. The prototype for transcriptional control is the lactose operon in E. coli. 

Kornberg, R. D. (1999). Eukaryotic transcriptional control. Trends Cell. Biol. 9(12), M46-M49. 

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.

Owen-Hughes T, Workman JL (1994) Experimental analysis of chromatin function in transcription control. Crit Rev Eukaryot Gene Expr 4 403 41... 

Transcription control is much more complex in eukaryotes (see p. 244). The number of transcription factors involved is larger, and in addition the gene activity is influenced by the state of the chromatin (see p. 238). 

The structure of RNA polymerase, the signals that control transcription, and the varieties of modification that RNA transcripts can undergo dffer among organisms, and particularly from prokaryotes to eukaryotes. Therefore, in this chapter, the discussions of prokaryotic and eukaryotic transcription are presented separately. 

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. 

Transcriptional control in eukaryotes can be accomplished at several levels. Chromatin structure can control transcription. The formation of so-called hypersensitive sites (sites where the DNA is not bound into nucleosomes) allows protein factors and RNA polymerase to access the DNA. This is necessary for transcription to occur, but hypersensitive sites are not enough. The removal of histone HI allows transcription to occur from a chromatin domain. Some protein factors (for example, TBF) may be bound to a promoter region even if the gene is not being transcribed. TBF also is necessary but not sufficient for transcription. 

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. 

Question Are there good examples of transcriptional control in eukaryotes ... 

Although bacteria lack TBP, archaea utilize a TBP molecule that is structurally quite similar to the eukaryotic protein. In fact, transcriptional control processes in archaea are, in general, much more similar to those in eukaryotes than are the processes in bacteria. Many components of the eukaryotic transcriptional machinery evolved from an ancestor of archaea. 

The major differences between prokaryotic and eukaryotic translation control mechanisms are related to the complexity of eukaryotic gene expression. Features that distinguish eukaryotic translation include mRNA export (spatial separation of transcription and translation), mRNA stability (the half-lives of mRNA can be modulated), negative translational control (the translation of certain mRNAs can be blocked by the binding of specific repressor proteins), initiation factor phosphorylation (mRNA translation rates are altered by certain circumstances when eIF-2 is phosphorylated), and translational frame-shifting (certain mRNAs can be frame-shifted so that a different polypeptide is synthesized). 

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