Epigenetic Control: Methylation, Acetylation & Heritability Revision Notes | A Level AQA Biology

1. The Hidden Layer of Gene Control

Your DNA sequence is fixed from the moment of fertilisation — yet identical twins can develop different diseases, different personalities, and different responses to the same drug. If the sequence is the same, what is changing? The answer lies in a layer of control sitting above the genome: epigenetics.

Epigenetics describes heritable changes in gene function that occur without any change to the underlying base sequence of DNA. The genes themselves are not altered — what changes is whether those genes can be read. Think of it like a dimmer switch on a light: the wiring (DNA) stays identical, but the switch position (epigenetic marks) determines how much light (gene expression) you get.

The word 'heritable' is doing important work in that definition. Epigenetic marks are copied when cells divide, so a daughter cell inherits not only the DNA sequence but also the pattern of chemical modifications on it. This is why epigenetic changes can have lasting consequences — and why they matter so much in development, ageing, and disease.

2. DNA Methylation: Silencing Genes with a Chemical Tag

Picture a stretch of DNA wound around a cluster of histone proteins — this is chromatin. Now imagine a small chemical group, a methyl group ($-CH_3$), being attached directly to a cytosine base in the DNA. That single addition can silence an entire gene. This process is called DNA methylation, and it is one of the two key epigenetic mechanisms you need to know for AQA.

Methylation typically occurs at regions called CpG sites, where cytosine sits next to guanine along the DNA strand. When methyl groups accumulate at the promoter region of a gene, they physically block transcription factors and RNA polymerase from binding. No binding means no transcription — the gene is effectively switched off.

Increased methylation therefore leads to decreased gene expression. The more methyl groups added to a region, the more tightly that region is silenced. Environmental factors — including diet, stress, and exposure to certain chemicals — can trigger changes in methylation patterns, which is how the environment feeds into epigenetic control.

A useful way to remember the direction of this effect: methylation mutes the gene. The more methyl groups present, the more the gene is muted. This is the mechanism by which many tumour-suppressor genes are silenced in cancer cells — their promoters become hypermethylated, switching off the very genes that would otherwise prevent uncontrolled cell division.

3. Histone Acetylation: Opening Up the Chromatin

DNA methylation acts directly on the DNA strand. The second major mechanism acts on the proteins that DNA is wrapped around. Histones are positively charged proteins, and DNA (being negatively charged) wraps tightly around them. The tighter this wrapping, the less accessible the DNA is to the transcription machinery.

Acetylation changes this. When acetyl groups ($-COCH_3$) are added to the histone proteins — specifically to lysine residues on their tails — the positive charge of the histone is reduced. This weakens the attraction between the histone and the negatively charged DNA, causing the chromatin to unwind and become less condensed. In this open configuration, transcription factors and RNA polymerase can access the DNA, and transcription proceeds.

For AQA, the key relationship to fix in your memory is this: decreased acetylation of histones inhibits transcription. When acetyl groups are removed (a process carried out by enzymes called histone deacetylases), the histones regain their positive charge, grip the DNA more tightly, and the chromatin condenses. The gene becomes inaccessible — silenced in the same functional outcome as increased methylation, but through a completely different molecular route.

4. How the Environment Drives Epigenetic Change

Earlier we established that epigenetic marks can be inherited. Now comes the crucial question: where do those marks come from in the first place? The answer is the environment. Changes in the environment — including diet, temperature, chemical exposure, and psychological stress — can alter the activity of the enzymes that add or remove methyl and acetyl groups. It's important to note that while environmental changes are a key driver of epigenetic modifications, these changes can also arise stochastically or during developmental processes without direct environmental influence.

A well-studied example is the effect of diet on methylation. Methyl groups are derived from dietary compounds such as folate and methionine. A diet low in these compounds can reduce the availability of methyl groups, leading to decreased methylation at certain loci and therefore increased expression of genes that would otherwise be silenced. Conversely, exposure to certain environmental toxins can trigger hypermethylation, silencing genes that should remain active.

The critical point for the specification is the causal chain: environmental change triggers a change in the pattern of methylation or acetylation, which inhibits transcription, which alters gene expression — all without touching the base sequence of the DNA. This is epigenetic control of gene expression in eukaryotes.

Worked example: Tracing the Epigenetic Pathway from Environment to Gene Silencing

Describe, in sequence, how an environmental change can lead to the silencing of a gene through epigenetic mechanisms. [5 marks]

1. An environmental change occurs — for example, exposure to a chemical, a change in diet, or psychological stress. — The environment does not alter DNA sequence; it alters the activity of enzymes that modify chromatin. [B1]
2. Increased methylation: methyl groups ($-CH_3$) are added to cytosine bases at the promoter region of the gene by DNA methyltransferase enzymes. — This is the direct chemical modification to the DNA itself. [B1]
3. Decreased acetylation: acetyl groups are removed from histone proteins by histone deacetylase enzymes, increasing the positive charge on histones. — Both routes can operate simultaneously or independently; either leads to gene silencing. [B1]
4. Chromatin condenses: the stronger histone-DNA attraction (from deacetylation) or the blocked promoter (from methylation) makes the DNA inaccessible. — Condensed chromatin physically prevents transcription factors and RNA polymerase from binding. [B1]
5. Transcription is inhibited. The gene is not expressed (or is expressed at a greatly reduced level), without any change to the DNA base sequence. — This is the definition of epigenetic control: heritable change in gene function, not gene structure. [B1]

Answer: Environmental change → increased methylation of DNA and/or decreased acetylation of histones → chromatin condenses → transcription factors and RNA polymerase cannot access the gene → transcription inhibited → gene silenced, with no alteration to the base sequence of DNA.

5. Heritability of Epigenetic Marks

One of the most striking features of epigenetic modifications is that they can be passed on. When a cell undergoes mitosis, the epigenetic marks on the parent cell's chromatin are reproduced in the daughter cells. This means that if an environmental stimulus causes a change in methylation or acetylation in one cell, all cells derived from it by division will carry the same altered pattern of gene expression.

At the organismal level, there is also evidence that some epigenetic marks can be transmitted across generations — from parent to offspring — though the mechanisms and extent of this transgenerational epigenetic inheritance are still an active area of research. For AQA purposes, the key claim is that epigenetic changes are heritable at the cellular level: daughter cells inherit the modified gene expression pattern.

This heritability is what distinguishes epigenetic changes from transient responses to the environment. A cell that briefly responds to a signal and then returns to its original state is not showing epigenetic change. An epigenetic change persists through cell division — it is copied and maintained in subsequent generations of cells.

6. Comparing Methylation and Acetylation: A Side-by-Side Analysis

Both methylation and acetylation are epigenetic mechanisms, but they act through different molecular targets and in different directions. Being able to compare them precisely is a skill the AQA mark scheme rewards — 'compare' questions require you to state both similarities and differences explicitly.

Notice the asymmetry: for methylation, it is increased methylation that silences genes. For acetylation, it is decreased acetylation that silences genes. This is the most common source of confusion in exam answers, and examiners are well aware of it.

7. Exam Technique and Mark-Winning Strategies

Epigenetics questions on AQA papers tend to use 'explain', 'describe', or 'evaluate' as command words. Each demands a different response structure. An 'explain' answer must include a causal chain — not just what happens, but why. An 'evaluate' answer requires you to weigh evidence and reach a conclusion.

When writing about methylation, always specify the direction: say 'increased methylation' rather than 'methylation occurs'. When writing about acetylation, always specify 'decreased acetylation' for silencing. Vague answers that say 'methylation changes gene expression' without specifying the direction will not score the mark.