Prokaryotic repressors

Several prokaryotic repressors can also be used in eukaryotes. Most notable is the tetracycline (TET) inducible expression system, which has had a... 

Fig. 3.3-1 Prokaryotic repressors can be exploited to control eukaryotic expression, (a) Repressor used to turn off transcription, (b) repressor-activator chimera used to turn-on gene expression. AD - activation domain.

Cro proteins are the prokaryotic repressors from bacteriophages X and 434. A helix-turn-helix motif, known to bind DNA, is common to repressors such as Cro proteins, trp repressor, and cl repressors. The Cro protein is a 66-... 

Activator proteins (and a few repressors) are important in eukaryotes, as they are in prokaryotes. The DNA sequences to which activator proteins bind in eiikaryotic DNA are called response elements. A few response elements are located within the promoter region (upstream promoter elements [UPE]), but most are outside the promoter and often clustered to form an enhancer region that allows control of gene expression by multiple signals (Figure 1-5-4). 

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. 

Repressors bind to specific sites on the DNA. In prokaryotic cells, such binding sites, called operators, are generally near a promoter. RNA polymerase binding,... 

One of the first metalloregulatory proteins to be characterized extensively is the prokaryotic MerR transcription factor (1, 6, 7), which acts either as a repressor (apo-protein) or an activator (holo-protein) of the mer operon encoding mercury resistance proteins (Fig. Ic). The —35 and —10 sequence elements of the mer promoter, binding sites for the RNA polymerase initiation complex, are separated by an unusually long distance that results in poor constitutive transcription. Apo-MerR binds to the DNA between these sequences and bends the DNA, which results in a slight increase in repression on the suboptimal promoter. It also recruits the RNA polymerase to the transcription start site where it waits in a stalled complex. Upon binding of... 

Busenlehner LS, Pennella MA, Giedroc DP. The SmtB/ArsR family of metalloregulatory transcriptional repressors structural insights into prokaryotic metal resistance. FEMS Microbiol. Rev. 2003 27 131-143. 

It interacts with activator and repressor proteins that modulate the rate of transcription initiation over a wide dynamic range. These proteins, which play a more prominent role in eukaryotes than in prokaryotes, are called transcrip-tion factors or trans-acting elements. Gene expression is controlled mainly at the level of transcription, as will be discussed in detail in Chapter 31. 

Despite these differences, some aspects of gene regulation in eukaryotes are quite similar to those in prokaryotes. In particular, activator and repressor proteins that recognize specific DNA sequences are central to many... 

E. An inducer is a small molecule that binds to and inactivates a repressor, which allows the sequence of DNA to be transcribed. An operon is a set of prokaryotic genes in close proximity that are coordinated as all off or aU on. An inducer may act to turn on the operon. One classic example is the lac operon. When allolactose is present, it serves as an inducer, and the operon is turned on, allowing proteins to be formed that metabohze lactose. 

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). 

---