Highlights Control of Bacterial Gene Expression

1. Cells must be able to respond to their environment. When food is low, cells must respond to that. Similarly, when food is abundant, they must act accordingly. The enzymes a cell will need in these two very different situations are considerably different.

2. Synthesis of proteins requires a lot of energy. Cells are "close to the edge" with respect to energy. They cannot afford to waste energy on things they do not need. Consequently, they must also control the synthesis of proteins according to the environmental cues they get.

3. We will consider two classes of genes. The first group is a set of genes needed by cells all the time. RNA polymerase is an example of a gene the cell needs to have almost all of the time, so it is almost always being transcribed. Genes like RNA polymerase that are being made almost all the time are classified as constitutive. Other genes are only made under special conditions. These genes are classified as inducible.

4. One way in which cells control protein synthesis is by controlling when and how transcription of a particular gene or set of genes is made. In bacteria. genes with common functions are clustered together in units called operons. Technically, an operon is a collection of genes under the same control and which are all made into one large mRNA. Operons are found in bacteria only - not in eukaryotes.

5. The lac operon in E. coli is one of the most studied sets of inducible genes in all of biology. The operon contain three genes that code for proteins necessary for the bacterium to break down lactose and use it as an energy source.

6. Lactose is not normally available to E. coli. Lactose is also known as milk sugar. The ideal situation has transcription of the lac operon turned on when lactose is present, but turned off when lactose is absent.

7. E. coli cells have a fairly simple system to turn on and turn off transcription of the lac operon. This is mediated mostly by action of a protein called the lac repressor. The lac repressor protein binds to the region of E. coli DNA near the operon. The region it binds to is the control headquarters (called a promoter). This control headquarters is where the RNA polymerase would normally bind to start transcription of the operon. When the lac repressor has bound to the control region, transcription of the operon is not possible.

8. It turns out that when there is no lactose in the cell, the repressor is always tightly bound to the control region, so E. coli is not making the enzymes in the lac operon.

9. The lac repressor protein, however, has a binding site for the sugar lactose. When lactose is present in the cell, it binds to the lac repressor. Binding of lactose to the lac repressor STOPS the repressor from binding to the control region of the lac operon.. As a consequence, the control region of the lac operon becomes open and available to the RNA polymerase, which makes mRNA of the operon. The mRNA is translated and the three enzymes for breaking down lactose are made. Thus, when lactose is present, the enzymes are made, but when lactose is absent, the enzymes are not made. This is a very simple control system for responding to the environment. In this case, the environmental factor is lactose. There are many others.

10. The lac repressor system is an example of a negative control system. That is, binding of the lac repressor to the control region negatively controls transcription of the operon. Other proteins act as positive regulators. An example is the CAP protein. This protein is able to bind to two things - cAMP and the control regions of genes in E. coli that help the cell respond to low energy situations. Thus, when there is low energy, cAMP is made. Binding of cAMP by CAP causes CAP to bind to the control regions. CAP can only bind to the control regions of target operons when cAMP is present. The reason we say CAP is a positive regulator is because binding of CAP to the control region helps to ACTIVATE the transcription of the operon