Lac operon regulation

What set of data originally led Jacob and Monod to suggest the existence of a repressor in lac operon regulation ... 

The existence of a repressor in lac operon regulation was first suggested by the results of studies of merodiploids. In merodiploids of the type i1 z I FCz+, Jacob and Monod were able to demonstrate that the i (inducible) allele is dominant to the i (constitutive) allele when on the same chromosome (cis) or on a different chromosome (trans) with respect to the z.+ allele. 

More than 30 years ago Jacob and Monod introduced the Escherichia coli lac operon as a model for gene regulation. The lac repressor molecule functions as a switch, regulated by inducer molecules, which controls the synthesis of enzymes necessary for E. coli to use lactose as an energy source. In the absence of lactose the repressor binds tightly to the operator DNA preventing the synthesis of these enzymes. Conversely when lactose is present, the repressor dissociates from the operator, allowing transcription of the operon. 

The Lac operon is but one example of the genetic adaptations which allow bacteria to respond to their environment. Other examples are to be found in amino acid metabolism, for example the TRP operon which regulates tryptophan metabolism. 

In accordance with the derivation of an expression for the regulation of the lac operon by Yagil and Yagil (83), the relationships discussed above between the relative rates of enzyme synthesis, a, and effector concentration, E, were evaluated. From... 

The well-investigated lactose operon of the bacterium Escherichial coli can be used here as an example of transcriptional control. The lac operon is a DNA sequence that is simultaneously subject to negative and positive control. The operon contains the structural genes for three proteins that are required for the utilization of lactose (one transporter and two enzymes), as well as control elements that serve to regulate the operon. 

B. The lac operon of E coli is a good model for regulation of prokaryotic gene expression in response to environmental cues (Figure 12-4). 

Figure 12-4. The lac operon. A simplified version of the lac operon illustrates how activity is regulated by availability of lactose as the sole carbon source. Repressor is the product of the lad regulatory gene. Lactose in the environment is converted to allolactose, which acts as the inducer. The ON state can only occur in the absence of glucose. With repressor inactive (unbound), RNA polymerase can transcribe the structural genes.

Despite this elaborate binding complex, repression is not absolute. Binding of the Lac repressor reduces the rate of transcription initiation by a factor of 10s. If the 02 and 03 sites are eliminated by deletion or mutation, the binding of repressor to CL alone reduces transcription by a factor of about 102. Even in the repressed state, each cell has a few molecules of /3-galactosidase and galactoside permease, presumably synthesized on the rare occasions when the repressor transiently dissociates from the operators. This basal level of transcription is essential to operon regulation. 

The mechanisms by which operons are regulated can vary significantly from the simple model presented in Figure 28-7. Even the lac operon is more complex than indicated here, with an activator also contributing to the overall scheme, as we shall see in Section 28.2. Before any further discussion of the layers of regulation of gene expression, however, we examine the critical molecular interactions between DNA-binding proteins (such as repressors and activators) and the DNA sequences to which they bind. 

The LexA repressor (Mr 22,700) inhibits transcription of all the SOS genes (Fig. 28-22), and induction of the SOS response requires removal of LexA. This is not a simple dissociation from DNA in response to binding of a small molecule, as in the regulation of the lac operon described above. Instead, the LexA repressor is... 

Negative Regulation Describe the probable effects on gene expression in the lac operon of a mutation in (a) the lac operator that deletes most of 0 (b) the lad gene that inactivates the repressor and (c) the promoter that alters the region around position -10. 

Regulation of the Three-Gene Cluster Known as the Lac Operon Occurs at the Transcription Level... 

Expression of the lac operon is regulated by controlling elements, which are separate from the structural genes. The controlling elements consist of a promoter locus, which is the site where RNA polymerase binds and initiates transcription the promoter locus also contains sites for the binding of a repressor and an activator. The i gene encodes the repressor, and the crp gene encodes the activator. 

The trp operon contains a cluster of five structural genes associated with tryptophan biosynthesis. Initiation of transcription of the trp operon is regulated by a repressor protein that functions similarly to the lac repressor. The main difference is that the trp repressor action is subject to control by the small-molecule effector, tryptophan. When tryptophan binds the repressor, the repressor binds to the trp operator. Thus, the effect of the small-molecule effector here is opposite to its effect on the lac operon. When tryptophan is present, there is no need for the enzymes that synthesize tryptophan. 

The explanation for the less than perfect match of most promoters to the consensus sequence is to be found in the need to regulate transcription. Transcriptional regulation is achieved in many instances by the selective improvement of the affinity of specific promoters for RNA polymerase. Such selective improvement is well illustrated in the case of regulation of the lac operon. 

It was Jacob and Monod in 1961 who proposed the operon model for the regulation of transcription. The lac operon is a good example of how operons work (Fig. 1). The operon model proposes three elements ... 

Positive and The lac operon is a good example of negative control (negative regulation) of... 

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