D2.2 Gene expression

Every cell in your body carries the same genome, yet a neuron, a muscle fibre and a white blood cell could hardly look more different. How? The answer is gene expression — the idea that having a gene is not the same as using it. Cells differ because they switch different sets of genes on and off, and they can change which genes are active in response to signals from inside and outside the body. This HL topic explores how that control works, from transcription factors that recruit the machinery of transcription, to chemical tags on DNA and its packaging proteins that can silence genes for the life of a cell and sometimes be passed to the next generation.

Regulating transcription: the role of transcription factors

The main point at which gene expression is controlled is transcription — whether a gene is copied into mRNA at all. This is governed by transcription factors, proteins that bind to specific DNA sequences and either help or hinder RNA polymerase.

• Activators bind to regulatory regions and increase the rate of transcription, often by helping RNA polymerase attach to the promoter.
• Repressors bind in ways that block or reduce transcription.

Because transcription factors recognise particular base sequences, a single signal can switch a whole set of related genes on or off at once. The syllabus uses the classic example of a hormone (such as a steroid) entering a cell, binding a receptor and acting as — or activating — a transcription factor, so that the appropriate genes are expressed only in the right cells at the right time. This is also how cells become differentiated: each cell type expresses a characteristic subset of the genome.

Epigenetics: changing expression without changing the sequence

Epigenetics refers to changes in gene expression that do not involve any change to the underlying DNA base sequence. Instead, reversible chemical modifications determine how accessible a gene is to the transcription machinery. Two mechanisms are central to the HL syllabus:

• DNA methylation: the addition of methyl (−CH₃) groups, typically to cytosine bases in the promoter region of a gene. Heavy methylation generally silences a gene by making it harder to transcribe.
• Histone modification: DNA is wound around proteins called histones. Chemical changes to these histones (such as acetylation) loosen or tighten the packaging. Loosely packed DNA is accessible and can be transcribed; tightly packed DNA is effectively switched off.

These chemical tags are collectively called the epigenome. Crucially, they can be copied when a cell divides, so a pattern of expression can be inherited by daughter cells — one reason a liver cell only ever makes more liver cells.

The environment and the epigenome

A major theme of this topic is that the environment can influence gene expression through epigenetic change. Factors such as diet, stress and exposure to chemicals can add or remove methyl groups and alter histones, switching genes on or off without mutating the DNA. This is how genetically identical individuals can end up different: identical (monozygotic) twins share the same DNA sequence yet accumulate different epigenetic marks over a lifetime, which helps explain why they grow steadily less alike and can differ in their susceptibility to disease.

Most epigenetic tags are erased between generations, but some appear to escape this resetting and be passed on, a phenomenon called transgenerational inheritance. Studies of populations that experienced famine, for example, suggest that the nutritional environment of one generation can be associated with health outcomes in their descendants. The IB treats such findings cautiously: they show that the line between nature and nurture is blurrier than once thought.

Reversibility and significance

Unlike a mutation, an epigenetic change is generally reversible — methyl groups can be removed and histone modifications undone — which makes the epigenome a flexible way to respond to changing conditions. This reversibility is medically important. Some cancers involve abnormal silencing of tumour-suppressor genes by methylation rather than by mutation, and because the DNA sequence is intact, drugs that reverse the methylation are being investigated as treatments.

For the exam, hold two ideas together. First, gene expression is controlled at multiple points but principally at transcription, through transcription factors. Second, epigenetic modifications (methylation and histone changes) layer an extra, environmentally responsive and often reversible level of control on top of the fixed DNA sequence. Together they explain how one genome can give rise to many cell types and how experience can leave a lasting, sometimes heritable, mark on which genes are used.