Negative vs Positive Control

• While the Trp operon is an example of repressible gene regulation and the Lac operon is an example of inducible gene regulation, both are examples of negative control of genes because both operons are shut "off" by an active repressor.
• Gene regulation would be positive; on the other hand, if an activator molecule turned the operon "on".
• The Lac operon is also an example of a positive control system and is turned on by the cAMP-CAP complex, as described below:
• E. coli can be described as a fussy eater.
• Its first choice at every meal is glucose because glucose supplies maximum energy for growth.
• Therefore, E. coli will only metabolize lactose if concentrations of glucose are low.
• For this to work, there must be a signal to tell the Lac operon that glucose is not available and to start transcribing the genes to metabolize lactose.
• This signal is a small molecule called cyclic AMP (cAMP).
• The amount of cAMP present in a cell is inversely proportional to the amount of glucose present.
• As a result, the absence of glucose results in an increase in cAMP in the cell.
• The following describes the situation where there is lactose but no glucose available to the cell:
• No glucose means high levels of cAMP.
• cAMP binds to a molecule known as CAP.
• CAP, when in association with cAMP, can bind to the promoter at the CAP binding site.
• Here, the cAMP-CAP complex stimulates transcription by helping RNA polymerase bind to the promoter.
• RNA polymerase has a weak affinity for the Lac promoter and will not bind without this help.
• Remember with lactose present so is allolactose.
• Allolactose binds to the repressor and prevents it from binding to the operator.
• Therefore, transcription and translation of the genes can occur.
• The following depicts what happens when glucose and lactose are both present for E. coli to metabolize:
• With glucose present, there is very little or no cAMP.
• It cannot bind to the CAP binding site.
• Without this complex, RNA polymerase cannot bind to the promoter and transcription cannot occur.
• Even though allolactose is present and blocks the action of the repressor, there is no transcription of the lac genes because glucose is present.

Fig. 25 . Overall structural elements of Lac Operon

Fig. 26. Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized

 

Fig. 27. Lactose present, glucose present (cAMO level low): little lac mRNA synthesized

 

REFERENCES:

Text Books:

1. Jeffery C. Pommerville. Alcamo's Fundamentals of Microbiology (Tenth Edition). Jones and Bartlett Student edition.

2. Gerard J. Tortora, Berdell R. Funke, Christine L. Case. Pearson - Microbiology: An Introduction. Benjamin Cummings.

3. J. Krebs, E.S. Goldstein, Stephen T. Kilpatrick. Lewin's Genes X. Jones and Bartlett Publishers.

Reference Books:

1. Lansing M. Prescott, John P. Harley and Donald A. Klein. Microbiology. Mc Graw Hill companies.

Other References:

1. http://www.nature.com/scitable/topic/gene-expression-and-regulation-15

2. http://ghr.nlm.nih.gov/handbook/howgeneswork/geneonoff