Year 12 Biology

Regulation of Gene Expression

Today you are looking at how cells control which genes are switched on, which genes are switched off, and why that matters for cell differentiation.

What to do: Work through the pack in order. Read the explanations, use the diagrams, and complete the questions in the spaces provided or in your notebook.

What this lesson is really asking

You already know how information in DNA can be used to make a protein. First, a gene is transcribed into mRNA. Then, that mRNA can be translated at a ribosome to build a polypeptide.

But cells do not use every gene all the time. That would be wasteful and chaotic. A muscle cell needs muscle-related proteins. A nerve cell needs proteins involved in signalling. A liver cell needs a different mix again.

So today’s question is not just “how does DNA become protein?” The better question is:

How does a cell control which genes are used, and which genes are kept quiet?

The next piece of the puzzle

This control is called gene regulation. Gene regulation controls when, where, and how much a gene is expressed.

This is why cells with the same DNA can become different cell types. They are not using different genetic instructions. They are using different parts of the same instruction set.

In this lesson, you will focus on two ways cells regulate gene expression:

1. Transcription factors

Proteins that help control whether RNA polymerase can transcribe a gene into mRNA.

2. Epigenetic tags

Chemical tags that affect gene expression by changing access to DNA, without changing the DNA sequence.

Key terms for today

Term Meaning for this lesson
Gene expression Using the information in a gene to make a functional product, usually a protein.
Gene regulation Controlling when, where, and how much a gene is expressed.
Cell differentiation The process where cells become specialised for different functions.
Transcription factor A protein that binds near a gene and affects transcription.
Epigenetic regulation Regulation of gene expression without changing the DNA base sequence.

Checkpoint 1

Answer this before moving on.

Question: If a nerve cell and a muscle cell contain the same DNA, why can they still look and function differently?

The switch idea

It can help to think of genes as being switched on or off. That is not a perfect analogy, because gene expression is often more like a dimmer switch than a simple light switch, but it is a useful starting point.

A gene can be highly expressed, weakly expressed, or not expressed at all. If a gene is not transcribed, then no mRNA is made from that gene. If no mRNA is made, that gene cannot be translated into a protein.

Gene regulation switch analogy
Figure: Gene regulation determines which genes are expressed and which genes are repressed.

This is the link back to protein synthesis. Turning down transcription means less mRNA. Less mRNA usually means less protein. Turning transcription off completely means that gene is not used to make a protein at that time.

Part 1

Transcription factors: deciding whether a gene gets used

The first control point is simple: before mRNA can be made, the cell has to allow transcription to begin.

Before transcription begins

Transcription does not happen just because a gene exists in the DNA. A gene can only be transcribed if the transcription machinery can reach the correct part of the DNA and begin making an mRNA copy.

The key enzyme here is RNA polymerase. RNA polymerase needs to bind near the start of the gene, close to the promoter region. If RNA polymerase can bind and move along the gene, an mRNA copy can be made. If RNA polymerase is blocked or not recruited properly, little or no mRNA is made from that gene.

Transcription factors are proteins that help control this step. Some transcription factors make RNA polymerase more likely to bind and begin transcription. Others make transcription less likely by blocking access or reducing how efficiently transcription begins.

The important point is that the cell is not changing the DNA sequence. It is changing whether that gene is actually used.

1

A transcription factor binds near a gene

A transcription factor is a regulatory protein. It binds near the promoter or start region of a gene, where transcription normally begins.

2

RNA polymerase is helped or blocked

The transcription factor changes how easily RNA polymerase can bind. If RNA polymerase is helped, transcription is more likely. If RNA polymerase is blocked, transcription is less likely or may not happen at all.

3

The amount of transcription changes

The gene may be copied into mRNA more often, less often, or not at all. This changes the amount of mRNA made from that gene.

4

Protein production can change

Translation uses mRNA as the message. If more mRNA is made, more protein may be produced. If less mRNA is made, less protein may be produced.

Put simply: transcription factors do not change the gene itself. They change how easily the gene is transcribed. That is why transcription factors can change gene expression without changing the DNA sequence.

Reducing expression

If a transcription factor blocks RNA polymerase from binding, the gene is not transcribed efficiently. Less mRNA is made from that gene, so less protein may be produced.

Increasing expression

If a transcription factor helps RNA polymerase bind or begin transcription, more mRNA may be made from that gene. This can increase the amount of protein produced.

Checkpoint 2

Use the explanation above to write a short, clear response.

Question: Describe how a transcription factor can reduce expression of a gene. Use the terms promoter, RNA polymerase, transcription, and mRNA.

Responding to signals

Gene expression can change in response to signals inside or outside the cell. For example, changes in glucose levels can affect expression of genes involved in insulin production.

The important point is this: the DNA sequence has not changed. The cell has changed which genes are being expressed. That is why gene regulation is so useful. It lets the same genome be used differently in different conditions.

Question: Explain the difference between changing a DNA sequence and changing gene expression.

Part 2

Epigenetics: changing expression without changing the code

The next layer of control is about access. Can the transcription machinery physically reach the gene?

The epigenome

The epigenome is a set of factors that affects which parts of the DNA are activated or repressed. Epigenetic factors can influence gene expression without changing the DNA base sequence.

Environmental and physiological factors can influence the epigenome. These may include diet, hormones, disease exposure, toxins, drugs, alcohol, exercise, stress, and signals from neighbouring cells.

Environmental factors affecting epigenetic control
Figure: Environmental and physiological factors can influence epigenetic control.

This does not mean the environment rewrites the gene sequence every time conditions change. It means environmental signals can affect which genes are easier or harder for the cell to express.

Question: Complete the sentence: Epigenetic regulation changes gene expression without changing...

DNA has to be packed

DNA is very long, so it has to be packaged inside the nucleus. It wraps around histone proteins to form structures called nucleosomes. This DNA-protein material is called chromatin.

How tightly DNA is packed affects whether genes can be transcribed. If the DNA is packed tightly, RNA polymerase and transcription factors may not be able to access the gene. If the DNA is packed more loosely, the gene is easier to access.

DNA wrapped around histones and chromatin structure
Figure: DNA wraps around histone proteins. The way chromatin is packed affects whether genes are accessible.

Euchromatin and heterochromatin

Now connect the packaging idea back to transcription. RNA polymerase and transcription factors need physical access to DNA. If a gene is buried in tightly packed chromatin, it is harder for the transcription machinery to reach it. If the chromatin is more open, the gene is easier to access and more likely to be transcribed.

There are two forms of chromatin you need to understand here: euchromatin and heterochromatin.

Euchromatin

Euchromatin is loosely packed chromatin. Because the DNA is more open, RNA polymerase and transcription factors can access genes more easily. Genes in euchromatin are more likely to be transcribed.

Heterochromatin

Heterochromatin is tightly packed chromatin. Because the DNA is condensed, transcription machinery cannot access genes as easily. Genes in heterochromatin are usually repressed or switched off.

This is why chromatin structure matters. The DNA sequence might still contain a gene, but if that gene is packed away in heterochromatin, the cell may not be able to use it. If the same gene is in euchromatin, it is physically easier for transcription to occur.

Euchromatin and heterochromatin comparison
Figure: Euchromatin is loosely packed and more accessible. Heterochromatin is tightly packed and usually repressed.
Feature Euchromatin Heterochromatin
Packing Loosely packed Tightly packed
Access to DNA Higher access because the chromatin is open Lower access because the chromatin is condensed
RNA polymerase More likely to access the start of the gene Less likely to access the start of the gene
Gene expression Genes are more likely to be active and transcribed Genes are usually repressed or switched off
Question: Explain why euchromatin is more likely to contain actively transcribed genes than heterochromatin. Your answer should mention chromatin packing, DNA accessibility, and RNA polymerase.

Histone modification

Chemical tags can attach to histone proteins. These tags can change how tightly DNA is wrapped around histones. Looser chromatin usually means genes are easier to access.

DNA methylation

A methyl group can attach near the start of a gene. If this blocks RNA polymerase from attaching, the gene cannot be transcribed.

DNA methylation

DNA methylation is one way a cell can reduce gene expression without changing the DNA sequence. A methyl group is a small chemical tag that can be added to DNA.

In this lesson, focus on what happens when methyl groups are added near the start of a gene. This region matters because RNA polymerase needs to bind near the start of a gene before transcription can begin. If methylation blocks RNA polymerase from binding, the gene cannot be copied into mRNA.

Without mRNA, the ribosome has no message to translate. That means little or no protein is produced from that gene. The DNA sequence is still the same, but the expression of the gene has changed.

DNA methylation and chromatin structure summary
Figure: DNA methylation and chromatin packing can affect whether transcription machinery can access a gene.
1

Methyl groups are added near the start of a gene

A methyl group is a chemical tag. When this tag is added near the region where transcription begins, it can affect whether the gene is accessible.

2

RNA polymerase cannot bind properly

RNA polymerase must bind near the start of the gene to begin transcription. If methylation blocks this binding, transcription cannot begin properly.

3

The gene is not transcribed into mRNA

If RNA polymerase cannot begin transcription, the DNA sequence of that gene is not copied into an mRNA message.

4

Little or no protein is made from that gene

Translation needs mRNA as the template. If little or no mRNA is made from the gene, little or no protein is produced from that gene.

Question: Turn the explanation above into a paragraph. Start with: DNA methylation can reduce gene expression because...

So what does this have to do with differentiation?

Cell differentiation happens when cells become specialised. Different cell types express different sets of genes. Transcription factors and epigenetic tags help control those patterns of expression.

A muscle cell can keep muscle-related genes active and accessible, while genes needed for other cell types remain switched off or harder to access. The DNA sequence is the same. The pattern of expression is different.

This is why gene regulation is central to multicellular life. The same genome can be used in different ways, allowing different cells to produce different proteins and perform different jobs.

Final checkpoint

Answer the question below in 8 to 10 sentences. Your answer should explain the mechanism, not just list terms.

Question: Explain how transcription factors and epigenetic tags regulate gene expression, and how this allows cells with the same DNA to differentiate into different cell types.
Planning help for the final checkpoint

A good answer should include:

  1. what gene regulation means
  2. how transcription factors affect RNA polymerase and transcription
  3. how chemical tags can affect chromatin structure
  4. the difference between euchromatin and heterochromatin
  5. how different patterns of gene expression allow cell differentiation

One last link forward

Next lesson, we will use this idea again. HOX genes are a group of genes involved in body patterning. Their protein products act as transcription factors, which means they regulate other genes during development.

So today's lesson is the foundation: before you can understand how genes shape body plans, you need to understand how genes are regulated.