The control of gene expression by transcription factors, the role of epigenetic modifications such as DNA methylation and histone modification, and how the environment can affect the phenotype.

What this dot point is asking

Edexcel wants you to explain how gene expression is controlled by transcription factors, describe epigenetic modifications such as DNA methylation and histone modification, and explain how the environment can affect the phenotype. The big idea in Biology B is that a single genome can give rise to many cell types and to phenotypes that respond to environment, so control of expression matters as much as the genes themselves.

Controlling transcription

Because only some genes are expressed in any given cell, transcription factors are a key way that cells of the same organism become different even though they share the same DNA. A transcription factor binds to the promoter region just upstream of a gene; once bound, it helps RNA polymerase attach (an activator) or blocks it (a repressor). Many transcription factors are themselves controlled by signals, so the cell can respond to its environment.

Hormones and transcription factors

Steroid hormones such as oestrogen are lipid-soluble, so they diffuse through the cell surface membrane and bind a receptor inside the cell. The hormone-receptor complex acts as a transcription factor, entering the nucleus and binding DNA to switch target genes on. This is a clean example of how an external signal changes which proteins a cell makes.

Epigenetic modifications

Histones are positively charged proteins that DNA wraps around to form chromatin. Adding negatively charged acetyl groups reduces the attraction between histones and DNA, opening the chromatin so genes can be transcribed. These modifications can be inherited when cells divide (so a liver cell produces more liver cells) and, in some cases, between generations.

Environment and phenotype

The environment (for example diet, stress, smoking or temperature) can cause epigenetic changes, so the same genotype can produce different phenotypes. This explains, in part, why genetically identical twins can differ and why some traits depend on lifestyle. Epigenetic change is reversible in principle, which is why it is a target for new cancer drugs that reactivate silenced tumour-suppressor genes.

Examples in context

Example 1. The agouti mouse. Genetically identical agouti mice can be yellow and obese or brown and lean depending on how heavily the agouti gene is methylated. When pregnant mice are fed a diet rich in methyl donors (such as folic acid and choline), more methylation silences the agouti gene in the offspring, producing brown, lean pups. The DNA sequence is unchanged, so this is a direct demonstration that diet alters phenotype through methylation.

Example 2. Tumour-suppressor silencing in cancer. In many cancers the promoter of a tumour-suppressor gene such as the one coding for a cell-cycle brake becomes hypermethylated and switched off, removing a control on cell division. Drugs that inhibit the methylating enzymes can reverse this silencing in some leukaemias, restoring the brake. This shows epigenetic change is reversible and clinically important.

Try this

Q1. Explain how DNA methylation can switch a gene off. [2 marks]

• Cue. Methyl groups added to the gene prevent transcription factors and RNA polymerase binding, so the gene is not transcribed.

Q2. Explain how the environment can affect the phenotype without changing the DNA sequence. [2 marks]

• Cue. Environmental factors cause epigenetic modifications such as methylation, which change which genes are expressed.