The diagram below outlines the ways in which gene expression (transcription and translation) can be controlled
- Regulation of transcription
- Transcription factors (Steroid hormones)
- Epigenetic changes
- Unregulated transcription (Cancer & gene expression)
- Regulation of translation
- RNA interference
Transcription Factors
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
In eukaryotes, transcription of target genes can be stimulated or inhibited when specific transcriptional factors move from the cytoplasm into the nucleus. The role of the steroid hormone, oestrogen, in initiating transcription.
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Transcription of genes controlled by transcription factors
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Transcription factors move to nucleus to bind to specific DNA sites of target genes (genes they want to control the expression of)
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Activators: Increase rate of transcription
- Bind to specific DNA sites promoter region (or enhancer region)
- Increase transcription by stimulating the binding of RNA polymerase to the promoter
- RNA polymerase binds to the promoter region of a gene to initiate transcription
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Repressors: Decrease rate of transcription
- Bind to specific DNA sequences called silencer regions
- Reduce transcription by preventing RNA polymerase binding to promoter
- As a result, RNA polymerase can’t bind to the promoter, so transcription is reduced or prevented
Oestrogen Receptor (TF)
The image below shows an example of how the steroid hormone oestrogen initiates transcription.
Mechanism for ER
- Oestrogen is lipid soluble so diffuses through phospholipid membrane
- It binds to the complementary site of the transcription factor (Oestrogen Receptor, ER) inside the cytoplasm.
- This binding of oestrogen causes the ER to change shape, along with its DNA binding site.
- ER can now move into the nucleus and bind to specific DNA sites near the start of the target gene (promoter region).
- This stimulates RNA polymerase and allows it to bind to the promoter region.
- This initiates transcription.
Epigenetics
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
Epigenetic control of gene expression in eukaryotes. Epigenetics involves heritable changes in gene function, without changes to the base sequence of DNA. These changes are caused by changes in the environment that inhibit transcription by: increased methylation of the DNA or decreased acetylation of associated histones.
Epigenetics is the heritable changes in gene expression, without changes to the base sequence of DNA. These changes are caused by environmental factors and affect the regulation of transcription.
Epigenome
The epigenome is a collection of chemical marks on your DNA and histone proteins that act like switches, telling your genes when, where, and how strongly to turn on or off, without changing the DNA sequence itself.
The epigenome is flexible and can respond to environmental changes such as stress and diet. This affects how genes are expressed.
- Directors cut analogy
A good way to think of it is that the genome is the script, and the epigenome is the director’s cut. Once the script has been agreed (fixed), the director can make edits to how they want the actors to play out the scene (I’m not a movie director so take this with a pinch of salt).
What are these chemical marks/modifications?
There are two main mechanisms of epigenetic control highlighted in the image below:
- Acetylation of histones
- Methylation of DNA
Acetylation of histones
Before discussing acetylation and deacetylation, it is important to understand that:
- Histone proteins have a positive charge (+)
- This is due to the presence of lysine residues on histone tails, which are positively charged.
- DNA has a negative charge (–)
- This is due to the phosphate groups in the DNA backbone, which are negatively charged.
- Adding or removing acetyl groups changes the charge on histones, affecting the attraction between histones and DNA.
Acetylation
- Involves the addition of an acetyl group to histone tails, using acetyl-CoA
- Acetylation neutralises (reduces) the positive charge on the histones
- This reduces the attraction between the positively charged histones and negatively charged DNA
- As a result, chromatin becomes less condensed (forming euchromatin)
- DNA becomes more accessible to transcription factors and RNA polymerase, allowing gene transcription to occur
Deacetylation
- Histone deacetylation involves the removal of acetyl groups from histones
- Removal of acetyl groups restores the positive charge on histones
- This increases the attraction between positively charged histones and negatively charged DNA
- Chromatin becomes more tightly packed (forming heterochromatin)
- DNA becomes less accessible to transcription factors and RNA polymerase
- As a result, transcription is reduced or inhibited, and gene expression is decreased
Methylation of DNA
- Involves the addition of a methyl group (–CH3) to DNA sequence (cytosine bases)
- This prevents transcription factors and RNA polymerase from binding to promoter
- This inhibits transcription and expression of the specific gene is reduced or silenced
Watch out: which one is methylated, and which is acetylated?
- DNA is methylated (methyl groups on cytosine bases)
- Histones are acetylated (acetyl groups on histone tails)
Examiners reject “methylation of histones” and “acetylation of DNA/genes”. Make sure you pair them up correctly.
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
The relevance of epigenetics on the development and treatment of disease, especially cancer.
Epigenetics plays a role in normal development but can also contribute to disease, such as cancer. For example, cancer cells may show increased DNA methylation of certain genes, causing these genes to be silenced. Potential epigenetic treatments include drugs that inhibit DNA methylation or histone deacetylation, which can lead to the reactivation of genes that have been silenced.
Further detail on cancer and epigenetics is covered in Gene Expression & Cancer
Epigenetics and inheritance
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Epigenetic markers (e.g. histone modification, methylation) can be passed from parent cell to daughter cells within the same individual. For example, when liver cells divide by mitosis, epigenetic markers are maintained in the daughter cells. This helps to preserve cell identity, so liver cells remain liver cells.
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Some evidence exists to say that epigenetic changes may also persist across generations and be passed to offspring, influencing the gene expression of the offspring. However, the evidence is limited and context dependent.
RNA Interference
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
In eukaryotes and some prokaryotes, translation of the mRNA produced from target genes can be inhibited by RNA interference (RNAi).
How does RNA interference work?
- A small RNA molecule, small interfering RNA (siRNA) can inhibit the translation of mRNA into polypeptide, silencing gene expression for specific proteins.
Mechanism for RNA interference
- Dicer enzyme breaks up double stranded RNA (dsRNA) into siRNA
- One strand of siRNA binds to a protein complex, RNA-induced silencing complex (RISC)
- The RISC-siRNA complex can bind to the target mRNA.
- The siRNA strand pairs with complementary bases on mRNA
- The enzyme within the protein complex cuts mRNA
- The mRNA is degraded and cannot be translated into a polypeptide, so the protein is not produced and the gene is not expressed
I thought RNA was single stranded?
I thought RNA was single stranded?
RNA is usually single stranded, such as mRNA. However, double stranded (dsRNA) can occur in some instances, e.g. viruses.
Watch out: what does siRNA bind to?
- siRNA binds to mRNA, NOT to the gene / DNA
- It blocks translation (not transcription)
- In exam questions involving a named gene, be specific. siRNA acts on the mRNA of that gene, not on a downstream protein.
Additional For Interest
RNA interference has potential therapeutic applications because it can be used to silence the expression of specific genes whose protein products cause or contribute to disease. https://www.alnylam.com/our-science/the-science-of-rnai
How this topic is tested
This analysis is based on past paper data from 2017 to 2025. It is intended for interest only and is not predictive of what will appear in future papers.
- Tested in 7 of 9 years (2017–2025): 24 question parts worth 54 marks.
- 15th most-examined topic overall by marks, 2nd in Unit 8.
Marks by year
Most-tested spec points
- Transcriptional Factors & Oestrogen: tested in 8 parts (15 marks)
- RNA Interference: tested in 5 parts (15 marks)
- Epigenetic Control of Gene Expression: tested in 5 parts (11 marks)
- Interpreting Gene Expression Data: tested in 2 parts (5 marks)
Also links to: Oncogenes, Tumour Suppressor Genes & Oestrogen, Membrane Structure & the Fluid-Mosaic Model, Factors Affecting Rate of Reaction.
Maths and practical skills
- Units and standard form (MS 0.1): e.g. 2021 P2 Q7.1
- Standard deviation and range (MS 1.10): e.g. 2021 P2 Q7.3
Exam Question Practice
Some cancers are caused by epigenetic changes to genes, rather than by mutations. Scientists are developing drugs that could reverse these changes.
Suggest and explain how these drugs could work.
(3 marks)
Hint
Which two types of gene are involved in cancer? How does methylation of DNA affect transcription? How does acetylation of histones affect it?
Mark Scheme
Max 3 marks
Which genes
- Drugs could decrease methylation of tumour suppressor genes (1 mark)
- Drugs could increase methylation of oncogenes (1 mark)
How it works
- Methylation of DNA inhibits transcription, so less methylation lets the gene be transcribed (1 mark)
- Acetylation of histones increases transcription, or less acetylation inhibits it (1 mark)
Also accepted / rejected
Tips
- Suggest drugs that decrease methylation of tumour suppressor genes, or increase methylation of oncogenes
- Explain the effect. Methylation of DNA inhibits transcription, and acetylation of histones increases it
- Say “transcription” or “expression”, not genes “switched on” or “off”. Epigenetic changes aren’t mutations
Some prostate cancers grow in response to the hormone testosterone. Testosterone binds to a receptor inside the cancer cells, which stimulates cell division. Some drugs used to treat these cancers have a similar shape to testosterone.
Suggest and explain how these drugs slow the growth of the cancer.
(3 marks)
Hint
Where could a drug with a similar shape to testosterone bind? What would that stop? Once testosterone binds, what does the receptor normally do in the nucleus?
Mark Scheme
- The drug binds to the testosterone receptor (1 mark)
- So testosterone can’t bind (1 mark)
- So the receptor doesn’t bind to the promoter as a transcription factor, or RNA polymerase isn’t activated (1 mark)
Explanation (not marked): The genes that stimulate cell division are transcribed less, so the cancer cells divide more slowly.
Also accepted / rejected
Not accepted
- “Active site” or “enzyme–substrate complex” (points 1 and 2)
- The drug binding to testosterone itself (point 1)
Tips
- The drug binds to the receptor, so testosterone can’t bind. The drug doesn’t bind to testosterone itself
- So the transcription factor doesn’t bind to the promoter, and RNA polymerase isn’t activated
- It’s a receptor, so don’t use “active site” or “enzyme–substrate complex”
Also accepted