Regulation of Gene Expression: Proteins must be generated at the correct time for a cell to operate effectively from information encoded in their DNA, all cells control or regulate protein production. Regulation of Gene expression is the process of turning on a gene to produce RNA and protein. Each cell, whether in a basic unicellular organism or a complex multicellular organism, regulates the frequency and manner its genes are expressed.

For this to happen, a mechanism must be in place to regulate when a gene is expressed to produce RNA and protein, how much of the protein is produced, and when the protein is no longer required. Regulation of gene expression, also known as gene regulation, refers to the various strategies that cells use to promote or reduce the output of specific gene products (protein or RNA). Let’s take a closer look at the regulation of gene expression.

What are Genes?

A gene is a section of DNA that codes for the production of a certain protein. The information database of the cell is DNA, which is found in the nucleus. It contains all of the necessary genetic instructions for producing the proteins that our cells require.

Each gene has its own set of instructions, which are usually in a coded format and are used to perform a certain function or produce a protein.

Fig: Genes

The genes, as mentioned above, are translated into mRNA before being transformed into a polypeptide chain. After that, a polypeptide is transformed into a protein. Gene expression is the result of all the hidden coding inside our genes expressing themselves as physical characteristics.

Gene Expression

It is a process in which the genetic codes of genes are used to control protein synthesis, which is necessary for our bodies to form cell structures. Structural genes are genes that carry information that is needed for amino acid sequencing.

Fig: Gene Expression

There are two main steps in this procedure:

1. Transcription– The messenger RNA is created in this stage with the help of RNA polymerase enzymes, resulting in the processing of mRNA molecules.
2. Translation– The primary purpose of mRNA is to direct protein synthesis, which leads to post-translational processing of the protein molecules.

Regulation of Gene Expression at Various Levels

Fig: Gene Regulation

The cell’s use of a number of procedures to either boost or reduce the production of a certain gene product is referred to as the regulation of gene expression (a protein or an RNA). In eukaryotes, the regulation could be exerted at, as explained below.

1. Replication level – Gene expression may be affected by mutations that occur during DNA replication.
2. Transcriptional level – The Repressors and activators can influence the transcription of a specific gene.
3. Post-transcriptional level – Post-transcriptional changes, such as RNA splicing, can result in gene expression.
4. Translational level – RNA interference mechanism, for example, can influence the translation of an mRNA molecule.

With the help of translation and transcription, gene’s genetic codes are used in managing the protein synthesis that is required for our body to produce the cell structures. Information is transferred from genes to proteins in this process.

Let’s use the Keratin genes as an example to comprehend this topic better. Keratin is a protein that has a role in developing our hair, nails, and skin. In most situations, these things continue to develop constantly while our hair, nails, and skin wear down over time. Excessive keratin production can result in a lot of hair on the skin, dry and hard skin, and thick and long nails. To avoid this, the expression of the keratin gene must be regulated.

Regulation of gene expression refers to the several processes by which our cells control the amount of protein produced by our genes.

Regulation of Gene Expression in Prokaryotes and Eukaryotes

Regulation of genes differs depending on whether the organism is prokaryotic or eukaryotic. Eukaryotes are multicellular and unicellular organisms with nuclei and other organelles within their cells, such as mammals, fungi, plants, and protists. Prokaryotes are single-celled organisms without a nucleus, such as bacteria. Because eukaryotes have a nucleus and prokaryotes do not, prokaryotic and eukaryotic transcription regulation is fundamentally different.

Fig: Regulation of Gene Expression in Prokaryotes and Eukaryotes

In the cytoplasm of prokaryotes, transcription and translation occur simultaneously, and transcriptional regulation occurs. Eukaryotic gene expression is regulated in two ways: in the nucleus during transcription and RNA processing and in the cytoplasm during protein translation. Protein post-translational changes may be used to regulate the process further.

Prokaryotic Transcription	Eukaryotic Transcription
It occurs in the cytoplasm.	It occurs within the nucleus.
The transcriptional unit has one or more genes	The transcriptional unit has just one gene
Transcription and translation are coupled	Transcription takes place in the nucleus, while translation takes place in the cytoplasm.
In the cytoplasm, RNAs are released and processed.	The nucleus processes RNA before releasing it into the cytoplasm.

How do Cells choose which Genes to Activate or ”Turn on”?

Gene regulation refers to how a cell manages the multiple genes in its genome that are activated (expressed) or “Turned On.” Even though practically all of the body’s cells carry the same DNA, gene regulation allows each cell type to have a unique collection of activated genes.  Numerous cell types have diverse sets of proteins due to these different gene expression patterns, making each cell type uniquely specialised to fulfill its task.

A microbial cell’s DNA contains hundreds to thousands of genes that do not all express at the same time. Only a few genes express and synthesise the necessary protein at any given moment. The other genes are currently silent and will express when needed. The environment in which they grow determines the amount of gene expression required. This demonstrates that genes have the ability to turn on and off. The genetic code states that proteins are made up of 20 distinct amino acids. Codons are responsible for the production of all proteins. As a result, all amino acid synthesis requires energy, which is inefficient because all of the amino acids that make up proteins are not required at the same time.

Different cell types express distinct sets of genes. However, depending on their surroundings and internal state, two separate cells of the same kind may have diverse gene expression patterns. In general, we may say that information from both within and outside the cell influences the gene expression pattern.

What Role do these Cues Play in a Cell’s Decision to Express Certain Genes?

Cells have molecular pathways that transform information into a change in gene expression, such as binding a chemical signal to its receptor. Consider how cells react to growth factors as an example.

Fig: Growth Factor Promoting Cell Division

1. The physical binding of the growth factor to a receptor protein on the cell surface allows it to recognise it.
2. When the growth factor binds to the receptor, it causes it to alter the shape, which sets off a chain of chemical reactions in the cell that activate transcription factors.
3. The transcription factors attach to certain DNA sequences in the nucleus and induce transcription of cell division-related genes.
4. These genes produce various proteins that cause the cell to divide (drive cell growth and proceed through the cell cycle).

It is only one example of how a cell can adjust gene expression in response to a source of information.
The activation of several targets, including transcription factors and non-transcription factor proteins, is involved in growth factor signalling.

Regulation of Gene Expression in Prokaryotes

Prokaryotes’ DNA is structured into a circular chromosome that sits in the cytoplasm of the cell. Proteins required for a given function or part of the same metabolic pathway are frequently encoded in operons. For example, in the bacteria E. coli, the trp operon contains all five of the genes required to produce the amino acid tryptophan. An operon’s genes are combined into a single mRNA molecule. It permits the genes to be controlled as a group: either expressed or none at all. Each operon only requires one regulatory region consisting of a promoter, which binds RNA polymerase, and an operator, which binds other regulatory proteins.

Three types of regulatory molecules can synthesise, affect operon expression in prokaryotic organisms.
A. Activators are proteins that boost a gene’s transcription.
B. Repressors are proteins that prevent a gene from being transcribed.
C. Inducers, on the other hand, are molecules that bind to repressors and render them inactive.

Operon Concept for Transcriptional Regulation

François Jacob and Jacques Monod proposed the Operon theory of gene control (1961). An operon is a group of structural genes whose expression is controlled by a single gene. A regulatory gene encodes a repressor that binds to the operator and inhibits operon transcription. The repressor is inactivated and dissociates from the operator in the presence of the inducer, allowing the operon to be expressed. As a result, a cis-acting operator and a trans-acting repressor control the operon’s expression.

Fig: Structure of Operon

1. Structural Gene: Any non-regulatory gene that codes for the production of a specific RNA, structural protein, or enzyme.
2. Regulatory Gene: The genes that code for regulator factors are known as regulatory genes. The expression of one or more genes is controlled by these regulatory factors.

Two examples of how these molecules regulate separate operons are shown below.

1. The Trp Operon: A Repressor Operon

Bacteria, like all cells, require amino acids to survive. E. coli may either swallow or generate tryptophan, an amino acid that it can obtain from the environment. E. coli must express a set of five proteins encoded by five genes when it wants to produce tryptophan. In the tryptophan (trp) operon, these five genes are positioned adjacent to each other.

A. E. coli does not need to synthesize tryptophan when it is present in the environment. Thus, the trp operon is turned off.
B. When tryptophan levels are low, the trp operon is activated, allowing the genes to be transcribed, proteins to be produced, and tryptophan to be synthesised.

Fig: The five genes that are needed to synthesize tryptophan in E. coli are located next to each other in the trp operon.

The operator is a DNA segment that lies between the promoter and the first trp gene. The repressor protein can attach to the DNA code contained in the operator. The amount of tryptophan in the cell regulates the repressor protein.

1. Two tryptophan molecules bind to the trp repressor when tryptophan is present in the cell. The repressor changes form and bind to the trp operator as a result of this.
2. The tryptophan–repressor complex binds to the operator, preventing the RNA polymerase from binding to and transcribing downstream genes.
3. As a result, when a cell has enough tryptophan, it stops generating more.

To block transcription, a repressor is bound to the operator in the negative control. A regulatory repressor protein is generally attached to the operator in negative inducible operons, preventing the transcription of the operon’s genes. When tryptophan is not present in the cell, the repressor has nothing to bind to. The repressor isn’t turned on and isn’t bound to the operator. As a result, RNA polymerase can transcribe the operon and cause tryptophan to be synthesised by the enzymes. As a result, if the cell lacks tryptophan, it synthesises tryptophan.

2. The lac Operon: An Inducer Operon

represented by the letter ‘Lac’ in Lac Operon. Lac Operon is an example of transcription control.

In many intestinal bacteria, including E. coli, it regulates the transcription of genes that code for enzymes involved in the transport and metabolism of lactose.

There are two types of genes in Lac Operon: structural genes and regulatory genes.

Lac Z, LacY, and Lac A are structural genes in Lac Operon that code for enzymes involved in lactose transport and metabolism.

1. lac Z: It codes for the enzyme -galactosidase, which hydrolyzes lactose to produce glucose and galactose, as well as converting lactose to its isomeric form, allolactose.
2. lac Y: It codes for the -galactoside permease enzyme, which is a transporter protein that helps lactose enter the cell.
3. lac A: The enzyme -galactoside transacetylase is encoded by this gene. This enzyme eliminates toxic -galactosides, glucosides, and lactosides from the cell by transferring an acetyl group from acetyl-CoA.

A repressor gene (Lac I), as well as promoter (P) and operator (O) genes, are all regulatory genes.

1. The transcription of structural genes is regulated by regulatory genes.
2. Lac I is a protein that encodes a repressor that binds to the operator sequence.
3. The promoter gene serves as an RNA polymerase binding site.

The lac operon in E. coli is regulated in a more sophisticated manner, involving both a repressor and an activator. When glucose concentrations are low, E. coli can utilise other carbohydrates, such as lactose, as a food source. Lactose is broken down by three proteins encoded by the lac operon’s three genes.

Lactose-digesting proteins aren’t required when lactose isn’t present. As a result, a repressor binds to the operator and inhibits the operon from being transcribed by RNA polymerase.

When lactose is present, it binds to the repressor and removes it from the operator. The lactose digesting genes can now be transcribed by RNA polymerase.

Fig: Transcription of the lac operon only occurs when lactose is present. Lactose binds to the repressor and removes it from the operator.

However, it’s more complicated than it seems. Even when the repressor is removed, the lac operon is only produced at low levels because E. coli prefers to eat glucose. But what happens when lactose is the only sugar present? The bacterium must now increase its synthesis of lactose-digesting proteins. Positive control of the lac operon is catabolite suppression. The result is an increase in transcription speed. It accomplishes this by acting as an activator for a protein known as catabolite activator protein (CAP).

When glucose levels fall, the cell begins to collect cyclic AMP (cAMP). cAMP binds to CAP, and the resulting complex binds to the promoter of the lac operon. It synthesises improves RNA polymerase’s capacity to bind to the promoter and speeds up gene transcription.

Fig: When there is no glucose, the CAP activator increases transcription of the lac operon. However, if no lactose is present, the operon is not activated.

Regulation of Gene Expression in Eukaryotes

Controlling gene expression in eukaryotes is more complicated and occurs at multiple levels. Because eukaryotic genes do not have operons, each gene must be controlled separately. Furthermore, eukaryotic cells have a much larger number of genes than prokaryotic cells. Gene expression can be controlled at any time after DNA is transcribed into mRNA and mRNA is translated into protein. Regulation is broken down into five categories for ease of use: epigenetic, transcriptional, post-transcriptional, translational, and post-translational.

Fig: Regulation of gene expression in eukaryotes can occur at five different levels.

Summary

The process of controlling which genes in a cell’s DNA is expressed is known as the regulation of genes (used to make a functional product such as a protein). Even though all cells in a multicellular organism have the same DNA, they may express substantially diverse sets of genes. A cell’s set of expressed genes defines the proteins and functional RNAs it carries, giving it its distinct characteristics. Gene expression in eukaryotes like humans involves multiple processes, and gene regulation can happen at any step. Many genes, on the other hand, are largely controlled at the transcriptional level.

Frequently asked questions (FAQs) on Regulation of gene expression

Q.1. What is the regulation of gene expression?
Ans: Gene regulation, also known as regulation of gene expression, refers to the various strategies that cells use to promote or reduce the output of specific gene products (protein or RNA).

Q.2. Which of the following can regulate gene expression in eukaryotes?
Ans: Gene expression in eukaryotic cells is regulated by repressors as well as by transcriptional activators.

Q.3. What is the importance of gene expression?
Ans: Gene expression regulation saves both energy and space. Because it would take a lot of energy for an organism to express every gene all of the time, it’s more energy efficient to turn them on only when they’re needed.

Q.4. At what level gene expression regulation can occur?
Ans: Gene regulation can happen at any stage throughout the transcription-translation process, but it most commonly happens during transcription. Transcription factors are proteins that can be triggered by other cells or environmental factors.

Q.5. What is the regulation of gene expression in eukaryotes?
Ans: Gene expression in eukaryotic cells is regulated by repressors as well as by transcriptional activators. Eukaryotic repressors, like their prokaryotic counterparts, bind to particular DNA sequences and prevent transcription.

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