Prokaryote gene regulation:

Gene regulation involves various types of mechanisms in prokaryotes that take place at different levels of gene expression. Based on their occurrence, they can be classified into three types of mechanisms such as:
 

1. Transcriptional control mechanisms
Several types of mechanisms fall into this category which can be further classified broadly into two major groups such as negative control mechanism and positive control mechanisms.
(i) Negative control:

    (a) Inducible systems:

These mechanisms involve the presence of an inhibitor or active repressor, which inhibits the transcription of the gene by binding to the DNA. An inducer protein is necessary for such mechanisms, so that it binds to the inhibitor that will in turn form inducer-repressor complex and thereby makes it impossible to bind to the DNA strands. As a result it induces the transcription of the particular gene and hence these mechanisms are also called inducible operons or systems.
Jacob and Monad in 1961 has proposed a model for explaining the inducible system, which is based on their study on the synthesis of Beta-galactosidase enzyme in E.coli bacteria. E.coli bacteria synthesize an enzyme called Beta-galactosidase, which is responsible for the hydrolysis of lactose to glucose and galactose. In the absence of lactose in the growing medium of E.coli, the production of Beta-galactosidase is remarkably reduced in the E.coli cells. This on and off switch mechanism is prevalently known as operon model however this concept was greatly modified since then

The Lac operon concept:

A Lac operon is constituted of three structural genes or cistrons, a regulator gene (i), a promoter gene (p) and an operator gene (o). The three structural genes are namely z, y, and a genes, where z codes for the enzyme , y codes for a membrane bound protein galactoside permease which helps in transport of metabolites into the cell and a codes for an enzyme called Beta-galactosidase transacetylase that transfers an acetyl group from acetyl CoA to Beta-galactosides. The regulator gene codes for the active repressor or the inhibitor protein.

The active repressor is synthesized by the regulator gene or Lac i gene, which has the tendency to bind to the operator region or Lac o and thereby blocks the RNA polymerase activity. The promoter region or Lac p is where the RNA polymerase binds and slides down transcribing towards structural genes, but only when it is not blocked by any repressor protein bound in its way. Here the lactose itself acts as the inducer compound for transcription. So, in the presence of lactose, lactose binds with the active repressor to make it inactive repressor, which will never be able to bind to the operator region anymore. Therefore, it helps the RNA polymerase enzyme to transcribe the structural genes.       

    (b) Repressible systems:

There are other systems like repressible systems which are quite reverse to the above mentioned model. Besides, the presence of high concentrations of the end product, which is also known as co-repressor, directly inhibits the production of the enzymes required for the biosynthesis of end product. Here the regulatory gene codes for a protein called aporepressor which binds with the co-repressor and forms a functional repressor molecule that which will eventually inhibit the transcription of all the genes responsible for the production of enzymes required for biosynthesis. The best example for this is regulation of histidine biosynthesis in salmonella typhimurium.  If the amino acid histidine is present in high concentrations in the medium, it starts acting as a co-repressor and terminates the synthesis of 10 enzymes required in the biosynthesis pathway of histidine.  

(ii) Positive control: 

The presence of some factors that enhance the attachment of RNA polymerase to the promoter sites is termed as positive gene regulation or control. The examples of this type of regulation are discussed below.

Glucose effect on Lac operon:

It is observed that in the presence of both glucose and lactose in the medium, the synthesis of b-galactosidase is dramatically brought down until the total glucose is utilized by the bacterium. We already know that the function of this enzyme is to convert lactose to glucose and galactose, which is again converted eventually into glucose by the activity of galactose operon. However it is found that inducer is not solely responsible for the structural genes to be transcribed but another cAMP-CAP complex is necessary. The presence of glucose in the medium regulates the concentration of cyclic AMP indirectly through glucose metabolism. Besides, the mechanism by which glucose regulates the cAMP is poorly understood.    

Tryptophan operon:

Tryptophan operon consists of five structural genes namely TrpE, TrpD, TrpC, TrpB and TrpA. These genes code for a set of five biosynthetic anabolic enzymes that are responsible for the synthesis of the amino acid tryptophan. Two other sequences called TrpL (leader) and Trpa (attenuator) are present adjacent to the TrpE. The promoter and the operator sequences are situated adjacent to the leader sequence but the regulator sequence TrpR is located away from these genes. The regulatory protein produced from the TrpR, which is also known as Trp aporepressor does not bind to the operator in the absence of tryptophan. In other words the tryptophan molecule and aporepressor unite to form an active repressor.     

1.       Translational control

Genes may be regulated at a level of translation and such a regulation of genes is termed as translational control. The average lifespan of an m-RNA is around 2 minutes in E.coli at 37o C. The m-RNA undergoes enzymatic degradation from the 5’ end to 3’ end. This type of enzymatic digestion is sometimes specific to certain nucleotides which make the m-RNA susceptible to enzymatic degradation.

2.       Post translational control

Genes are also regulated even after they are expressed and proteins are synthesized. Here the enzyme synthesis is not at all affected but the enzyme activity is itself inhibited. The best example for this type of regulation is isoleucine synthesis in E.coli. When the end product i.e. isoleucine is supplied to the medium, it blocks the enzymes of the threonine – isoleucine pathway. Therefore this type of enzymatic activity regulation is also called feedback inhibition. Further, this regulation occurs after the translational process and hence this is termed as post translational regulation or control.