Regulation of gene expression refers to a very broad term that may occur at various levels. Considering that gene expression results in the formation of a polypeptide, it can be regulated at several levels. In eukaryotes, the regulation could be exerted at
The genes in a cell are expressed to perform a particular function or a set of functions. For example, if an enzyme called beta-galactosidase is synthesised by E. coli, it is used to catalyse the hydrolysis of a disaccharide, lactose into galactose and glucose; the bacteria use them as a source of energy. Hence, if the bacteria do not have lactose around them to be utilised for energy source, they would no longer require the synthesis of the enzyme beta-galactosidase. Therefore, in simple terms, it is the metabolic, physiological or environmental conditions that regulate the expression of genes. The development and differentiation of embryo into adult organisms are also a result of the coordinated regulation of expression of several sets of genes.
In prokaryotes, control of the rate of transcriptional initiation is the predominant site for control of gene expression. In a transcription unit, the activity of RNA polymerase at a given promoter is in turn regulated by interaction with accessory proteins, which affect its ability to recognise start sites. These regulatory proteins can act both positively (activators) and negatively (repressors). The accessibility of promoter regions of prokaryotic DNA is in many cases regulated by the interaction of proteins with sequences termed operators. The operator region is adjacent to the promoter elements in most operons and in most cases the sequences of the operator bind a repressor protein. Each operon has its specific operator and specific repressor. For example, lac operator is present only in the lac operon and it interacts specifically with lac repressor only.
The Lac operon
The elucidation of the lac operon was also a result of a close association between a geneticist, Francois Jacob and a biochemist, Jacque Monod. They were the first to elucidate a transcriptionally regulated system. In lac operon (here lac refers to lactose), a polycistronic structural gene is regulated by a common promoter and regulatory genes. Such arrangement is very common in bacteria and is referred to as operon. To name few such examples, lac operon, trp operon, ara operon, his operon, val operon, etc.
The lac operon consists of one regulatory gene (the \(i\) gene – here the term \(i\) does not refer to inducer, rather it is derived from the word inhibitor) and three structural genes ( \(z, y\), and \(a\) ). The \(i\) gene codes for the repressor of the lac operon. The \(z\) gene codes for beta-galactosidase ( \(\beta\)-gal), which is primarily responsible for the hydrolysis of the disaccharide, lactose into its monomeric units, galactose and glucose. The \(y\) gene codes for permease, which increases permeability of the cell to \(\beta\)-galactosides. The \(a\) gene encodes a transacetylase. Hence, all the three gene products in lac operon are required for metabolism of lactose. In most other operons as well, the genes present in the operon are needed together to function in the same or related metabolic pathway (Figure 5.14).
Lactose is the substrate for the enzyme beta-galactosidase and it regulates switching on and off of the operon. Hence, it is termed as inducer. In the absence of a preferred carbon source such as glucose, if lactose is provided in the growth medium of the bacteria, the lactose is transported into the cells through the action of permease (Remember, a very low level of expression of lac operon has to be present in the cell all the time, otherwise lactose cannot enter the cells). The lactose then induces the operon in the following manner.
The repressor of the operon is synthesised (all-the-time – constitutively) from the \(i\) gene. The repressor protein binds to the operator region of the operon and prevents RNA polymerase from transcribing the operon. In the presence of an inducer, such as lactose or allolactose, the repressor is inactivated by interaction with the inducer. This allows RNA polymerase access to the promoter and transcription proceeds (Figure 5.14). Essentially, regulation of lac operon can also be visualised as regulation of enzyme synthesis by its substrate.
Remember, glucose or galactose cannot act as inducers for lac operon. Can you think for how long the lac operon would be expressed in the presence of lactose?
Regulation of lac operon by repressor is referred to as negative regulation. Lac operon is under control of positive regulation as well, but it is beyond the scope of discussion at this level.
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