Prokaryotic Gene Regulation

Introduction

If all cells have the same DNA content, and the DNA of a cell specifies its activities (what enzymes it makes) and characteristics (what effect these enzymes have), why aren't all cells the same? We know, however, that there are different cell types in our bodies, and that the activities of these cells changes with time. The hormone-producing cells in the pituitary gland only produce growth hormone during childhood and adolescence. These same cells remain in the pituitary in adulthood, but they don't function to produce growth hormone. How do they know when they are needed or not needed?

This question as it applied to large, compex organisms like humans was very daunting for scientists in the first half of the 20th century. Francois Jacob and Jacques Monod approached the problem from a more basic and simple perspective. How did single-celled prokaryotes like E. coli know how to respond to their environments? Each environmental cue generates a specific response, with specific proteins and reactions. For example, a bacterium can use several different sources of nitrogen. Some bacteria can incorporate diatomic nitrogen gas from the air, or incoprporate ammonia from their surroundings, or break the amine group from the end of an amino acid like glutamine. It is much easier and less energy costly for the cell to use the nitrogen from glutamine than to fix nitrogen gas from the air. These two processes rquire very different enzymes to allow them to occur. If there is glutamine around, the cell should be able to shut off the enzymes that are involved in incorporation of nitrogen gas. In fact, it shouldn't have to waste the energy to synthesize these enzymes at all. How can the cell "turn off" the synthesis of proteins from its DNA, when the moment calls for it?

The cell could somehow selectively inhibit transcription of the gene. The mRNA for this gene would never be made.
The cell could selectively degrade the mRNA as soon as it was made, preventing it from being translated into protein.
The cell could selectively prevent translation on an otherwise stable mRNA.
The cell could selectively degrade the translated protein so that it couldn't waste energy trying to catalyse reactions that the cell has no need for at that time.

In all these cases, the cell has to have some way of shutting off the unwanted protein selectively and leaving on the other genes in the cell. As you can imagine, in terms of energy cost, it is better to shut off the process as early as possible, so that no energy is wasted in mRNA and protein synthesis. This type of early-intervention control is called transcriptional regulation, since expression of the gene is regulated at the level of mRNA synthesis, or transcription.

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