Overview: Gene regulation in bacteria

Overview of operons, regulatory DNA sequences, & regulatory genes. Repressor & activator proteins.

Key points:

  • Bacterial genes are often found in operons. Genes in an operon are transcribed as a group and have a single promoter.
  • Each operon contains regulatory DNA sequences, which act as binding sites for regulatory proteins that promote or inhibit transcription.
  • Regulatory proteins often bind to small molecules, which can make the protein active or inactive by changing its ability to bind DNA.
  • Some operons are inducible, meaning that they can be turned on by the presence of a particular small molecule. Others are repressible, meaning that they are on by default but can be turned off by a small molecule.

Introduction

We tend to think of bacteria as simple. But even the simplest bacterium has a complex task when it comes to gene regulation! The bacteria in your gut or between your teeth have genomes that contain thousands of different genes. Most of these genes encode proteins, each with its own role in a process such as fuel metabolism, maintenance of cell structure, and defense against viruses.
Some of these proteins are needed routinely, while others are needed only under certain circumstances. Thus, cells don't express all the genes in their genome all the time. You can think of the genome as being like a cookbook with many different recipes in it. The cell will only use the recipes (express the genes) that fit its current needs.

How is gene expression regulated?

There are various forms of gene regulation, that is, mechanisms for controlling which genes get expressed and at what levels. However, a lot of gene regulation occurs at the level of transcription.
Bacteria have specific regulatory molecules that control whether a particular gene will be transcribed into mRNA. Often, these molecules act by binding to DNA near the gene and helping or blocking the transcription enzyme, RNA polymerase. Let's take a closer look at how genes are regulated in bacteria.

In bacteria, genes are often found in operons

In bacteria, related genes are often found in a cluster on the chromosome, where they are transcribed from one promoter (RNA polymerase binding site) as a single unit. Such a cluster of genes under control of a single promoter is known as an operon. Operons are common in bacteria, but they are rare in eukaryotes such as humans.
Diagram illustrating what an operon is. At the top of the diagram, we see a bacterial cell with a circular bacterial chromosome inside it. We zoom in on a small segment of the chromosome and see that it is an operon. The DNA of the operon contains three genes, Gene 1, Gene 2, and Gene 3, which are found in a row in the DNA. They are under control of a single promoter (site where RNA polymerase binds) and they are transcribed together to make a single mRNA that has contains sequences coding for all three genes. When the mRNA is translated, the three different coding sequences of the mRNA are read separately, making three different proteins (Protein 1, Protein 2, and Protein 3).
Note: The operon does not consist of just the three genes. Instead, it also includes the promoter and other regulatory sequences that regulate expression of the genes.
In general, an operon will contain genes that function in the same process. For instance, a well-studied operon called the lac operon contains genes that encode proteins involved in uptake and metabolism of a particular sugar, lactose. Operons allow the cell to efficiently express sets of genes whose products are needed at the same time.
No, not all of them. Some genes in bacteria are transcribed individually. These individually transcribed genes each have their own promoter and other regulatory DNA sequences. That is, the features described below for operons also apply to genes in bacteria that are not located in operons.

Anatomy of an operon

Operons aren't just made up of the coding sequences of genes. Instead, they also contain regulatory DNA sequences that control transcription of the operon. Typically, these sequences are binding sites for regulatory proteins, which control how much the operon is transcribed. The promoter, or site where RNA polymerase binds, is one example of a regulatory DNA sequence.
Diagram illustrating that the promoter is the site where RNA polymerase binds. The promoter is found in the DNA of the operon, upstream of (before) the genes. When the RNA polymerase binds to the promoter, it transcribes the operon and makes some mRNAs.
Most operons have other regulatory DNA sequences in addition to the promoter. These sequences are binding sites for regulatory proteins that turn expression of the operon "up" or "down."
  • Some regulatory proteins are repressors that bind to pieces of DNA called operators. When bound to its operator, a repressor reduces transcription (e.g., by blocking RNA polymerase from moving forward on the DNA).
Diagram illustrating how a repressor works. A repressor protein binds to a site called on the operator. In this case (and many other cases), the operator is a region of DNA that overlaps with or lies just downstream of the RNA polymerase binding site (promoter). That is, it is in between the promoter and the genes of the operon. When the repressor binds to the operator, it prevents RNA polymerase from binding to the promoter and/or transcribing the operon. When the repressor is bound to the operator, no transcription occurs and no mRNA is made.
  • Some regulatory proteins are activators. When an activator is bound to its DNA binding site, it increases transcription of the operon (e.g., by helping RNA polymerase bind to the promoter).
Diagram illustrating how an activator works. The activator protein binds to a specific sequence of DNA, in this case immediately upstream of (before) the promoter where RNA polymerase binds. When the activator binds, it helps the polymerase attach to the promoter (makes promoter binding more energetically favorable). This causes the RNA polymerase to bind firmly to the promoter and transcribe the genes of the operon much more frequently, leading to the production of many molecules of mRNA.
Where do the regulatory proteins come from? Like any other protein produced in an organism, they are encoded by genes in the bacterium's genome. The genes that encode regulatory proteins are sometimes called regulatory genes.
As a general rule, no, they aren't. They're typically encoded elsewhere in the genome and expressed under control of their own promoter and regulatory sequences. Once the gene has been expressed to make a protein, that protein floats around in the cell and can bind to the DNA of the target operon.
However, it's certainly possible for a regulatory gene to be found in the same operon that its protein product regulates. When the product of a regulatory gene regulates the expression of the gene itself, there is the potential for formation of a positive or negative feedback loop.
For instance, if an activator protein increases its own expression, a positive feedback loop is formed, causing progressively larger amounts of activator to be produced. For a real-life example in which this takes place, see the article on autoinducers in quorum sensing.
Many regulatory proteins can themselves be turned "on" or "off" by specific small molecules. The small molecule binds to the protein, changing its shape and altering its ability to bind DNA. For instance, an activator may only become active (able to bind DNA) when it's attached to a certain small molecule.
Diagram illustrating how a hypothetical activator's activity could be modulated by a small molecule. When the small molecule is absent, the activator is "off" - it takes on a shape that makes it unable to bind DNA. When the small molecule that activates the activator is added, it binds to the activator and changes its shape. This shape change makes the activator able to bind its target DNA sequence and activate transcription.

Operons may be inducible or repressible

Some operons are usually "off," but can be turned "on" by a small molecule. The molecule is called an inducer, and the operon is said to be inducible.
  • For example, the lac operon is an inducible operon that encodes enzymes for metabolism of the sugar lactose. It turns on only when the sugar lactose is present (and other, preferred sugars are absent). The inducer in this case is allolactose, a modified form of lactose.
Other operons are usually "on," but can be turned "off" by a small molecule. The molecule is called a corepressor, and the operon is said to be repressible.
  • For example, the trp operon is a repressible operon that encodes enzymes for synthesis of the amino acid tryptophan. This operon is expressed by default, but can be repressed when high levels of the amino acid tryptophan are present. The corepressor in this case is tryptophan.
These examples illustrate an important point: that gene regulation allows bacteria to respond to changes in their environment by altering gene expression (and thus, changing the set of proteins present in the cell).

Some genes and operons are expressed all the time

Many genes play specialized roles and are expressed only under certain conditions, as described above. However, there are also genes whose products are constantly needed by the cell to maintain essential functions. These housekeeping genes are constantly expressed under normal growth conditions ("constitutively active"). Housekeeping genes have promoters and other regulatory DNA sequences that ensure constant expression.
This article is licensed under a CC BY-NC-SA 4.0 license.

References:

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