How cells with identical DNA become muscle, nerve, or blood cells — and how expression is regulated at every level.
Before you learn the content, have a go at this problem. It's okay to find it hard — struggling builds stronger understanding.
Identical twins share 100% of their DNA. Yet one twin develops Type 2 diabetes at age 40 while the other remains healthy. Suggest how gene expression could explain this difference.
Write your best answer with no support. Consider what could change gene activity without altering the DNA sequence itself.
Use these prompts to structure your answer:
Complete the paragraph:
Although the twins have the same _______ (DNA sequence), their _______ patterns may differ. Environmental factors such as _______ and _______ can cause _______ changes — modifications that alter gene expression without changing the DNA sequence. For example, _______ groups may be added to DNA, which _______ transcription of certain genes. This means one twin may express genes for insulin resistance while the other does not.
Not all genes are active in every cell. Transcription factorsProteins that bind to specific DNA sequences near a gene to control whether RNA polymerase can transcribe it. are proteins that regulate which genes are switched on or off by controlling whether RNA polymerase can bind and begin transcription.
Every gene has a promoterA region of DNA upstream of a gene where RNA polymerase and transcription factors bind to initiate transcription. region — a specific DNA sequence just before (upstream of) the coding region. RNA polymerase cannot bind to the promoter alone; it needs transcription factors to assemble first.
Some genes also have enhancerRegulatory DNA sequences, often far from the gene, that increase the rate of transcription when activator proteins bind to them. sequences. These can be thousands of base pairs away from the gene, but when activator proteins bind to them, the DNA loops so the enhancer comes close to the promoter, boosting transcription.
Questions often ask you to explain how transcription factors initiate transcription. Key steps: (1) TFs bind to the promoter region, (2) this forms a transcription initiation complex, (3) RNA polymerase can then bind, (4) transcription of the gene begins.
Activators increase transcription by binding to enhancers and recruiting RNA polymerase. Repressors decrease transcription by blocking TF binding or preventing the initiation complex from forming. This is how different cell types express different genes.
Once pre-mRNA is transcribed, it still needs processing before it can be translated. This is another level where gene expression can be regulated.
Pre-mRNA contains both exonsCoding sequences of a gene that are expressed in the final mRNA. Exons are joined together after splicing. (coding regions) and intronsNon-coding “intervening” sequences within a gene that are removed (spliced out) during RNA processing. (non-coding regions). During RNA processing, introns are removed by a complex called the spliceosomeA large molecular machine made of snRNPs (small nuclear ribonucleoproteins) that catalyses the removal of introns from pre-mRNA., and the remaining exons are joined together.
The key insight: different combinations of exons can be joined together from the same pre-mRNA. This means one gene can produce multiple different proteins. This is called alternative RNA splicing.
Remember: exons are expressed (they stay). Introns are intervening (they are removed). The spliceosome is the molecular machine that does this work.
EpigeneticsHeritable changes in gene expression that do not involve changes to the DNA base sequence. Caused by chemical modifications to DNA or histone proteins. literally means “above genetics”. These are modifications that change how genes are expressed without altering the DNA base sequence. They can be inherited through cell division and sometimes between generations.
A methyl group (-CH3) is added to cytosineOne of the four DNA bases. When methylated (5-methylcytosine), the gene associated with that region is typically silenced. bases in DNA, usually where cytosine is followed by guanine (CpG sites). This is catalysed by DNA methyltransferase enzymes.
Effect: Methylation typically silences gene expression because:
Methylation patterns can be passed on during DNA replication — this is how differentiated cells “remember” which genes to express.
DNA is wound around histoneProtein “spools” that DNA wraps around to form nucleosomes. Chemical modifications to histones alter how tightly DNA is packaged. proteins to form nucleosomes. The “tails” of histones can be chemically modified, changing how tightly DNA is packaged.
| Modification | Effect on Chromatin | Effect on Gene Expression |
|---|---|---|
| Acetylation | Loosens chromatin (euchromatin) | Increases transcription — DNA is accessible to RNA polymerase |
| Deacetylation | Tightens chromatin (heterochromatin) | Decreases transcription — DNA is tightly wound and inaccessible |
| Methylation | Can loosen or tighten depending on position | Can activate or repress — depends on which amino acid is methylated |
Epigenetic modifications explain how differentiated cells maintain their identity. A liver cell keeps liver-specific genes active and other genes methylated/silenced. These patterns are copied when the cell divides, so daughter cells remain liver cells.
Not all RNA codes for proteins. Non-coding RNA (ncRNA)RNA molecules that are not translated into protein but have regulatory roles in gene expression. Includes miRNA, siRNA, and lncRNA like Xist. plays important regulatory roles in controlling gene expression.
Female mammals have two X chromosomes (XX) while males have one (XY). To prevent a “double dose” of X-linked gene products, one X chromosome in each female cell is inactivated early in embryonic development.
The process is controlled by a long non-coding RNA called XistX-inactive specific transcript — a long non-coding RNA produced from the X chromosome that coats the chromosome from which it is transcribed, triggering its inactivation. (X-inactive specific transcript):
The choice of which X to inactivate is random in each cell. This means female mammals are mosaics — some cells express the maternal X and some express the paternal X.
In the giant polytene chromosomes of Drosophila and Chironomus larvae, regions of active transcription can be seen as “chromosome puffsRegions of decondensed, actively transcribing DNA visible in polytene chromosomes. Different puffs appear in different cell types, showing differential gene expression.” — areas where the chromatin is decondensed and genes are being actively transcribed.
Different cell types show different puffing patterns, providing direct visual evidence that different genes are expressed in different cell types. This is controlled by epigenetic mechanisms.
promoter • enhancer • introns • splicing • methylation • acetylation • Barr body • Xist
Drag the steps into the correct order to show how a gene is expressed and regulated.
Explain how epigenetic mechanisms allow cells with identical DNA to become specialised for different functions. Include reference to DNA methylation, histone modification, and the role of transcription factors. [6 marks]
Use the prompts below to explain how cells become specialised:
Complete this model answer:
All cells contain the same _______ but not all genes are expressed in every cell. Transcription factors are proteins that bind to the _______ region of a gene and allow _______ to begin transcription.
Genes that are not needed in a particular cell type can be silenced by DNA _______, where -CH3 groups are added to _______ bases. This prevents transcription factors from _______.
Genes that ARE needed can be activated by histone _______, which _______ the chromatin so RNA polymerase can access the DNA. These epigenetic patterns are _______ when cells divide, so daughter cells maintain the same specialisation.
State two ways in which epigenetic changes differ from mutations.
1. Epigenetic changes do not alter the DNA base sequence / mutations change the base sequence. (1)
2. Epigenetic changes are often reversible / mutations are permanent changes to the DNA. (1)
Explain how alternative RNA splicing allows one gene to code for more than one protein.
1. A gene contains both exons (coding sequences) and introns (non-coding sequences). (1)
2. Pre-mRNA is transcribed and contains both exons and introns. (1)
3. The spliceosome removes introns, but different combinations of exons can be retained / joined together. (1)
4. Different mature mRNA molecules are produced, which are translated into different polypeptides / proteins. (1)
Discuss the role of epigenetic modifications in controlling gene expression and their significance in cell differentiation. Include reference to DNA methylation, histone modification, and non-coding RNA.
DNA methylation: Methyl groups (-CH3) are added to cytosine bases at CpG sites. This prevents transcription factors from binding to the promoter region, silencing the gene. Methylation patterns are inherited during cell division, maintaining cell identity. (2)
Histone modification: Acetylation of histone tails loosens chromatin (euchromatin), making DNA accessible to RNA polymerase and transcription factors, activating genes. Deacetylation tightens chromatin (heterochromatin), silencing genes. Different patterns of histone modification in different cell types ensure only appropriate genes are expressed. (2)
Non-coding RNA: ncRNA such as Xist plays a role in gene regulation. Xist coats one X chromosome in female cells, recruiting proteins that add repressive epigenetic marks, condensing it into a Barr body. This is dosage compensation — ensuring females do not produce double the X-linked gene products compared to males. This demonstrates how non-coding RNA coordinates large-scale gene silencing. (2)
For “discuss” questions, cover each named topic with: (1) a clear description of the mechanism, (2) its effect on gene expression, (3) its significance/application. Use correct terminology throughout.
Three quick questions before you go:
1. Describe the role of transcription factors in gene expression.
2. Explain how one gene can produce multiple different proteins.
3. Describe how DNA methylation and histone acetylation have opposite effects on gene expression.