20.4 - Epigenetic Control of Gene Expression
- 1How epigenetic changes can control gene expression
- 2Methods of epigenetic control and their effects on genes
- 3Inheritance of epigenetic changes
- 4The role of epigenetics in disease and potential drug therapies
- 5The effect of RNA interference on gene expression
How epigenetics can control gene expression
In eukaryotes, gene expression can be controlled through epigenetics. These are heritable chemical modifications to DNA or histones (DNA-binding proteins) that do not change the DNA base sequence itself.
DNA, being negatively charged, wraps around positively charged histone proteins to form chromatin. The epigenome is a layer of chemical tags, called epigenetic marks, that cover this DNA-histone complex.
How the epigenome affects gene expression:
- Epigenetic marks are attached to or removed from DNA or histones.
- This can change the shape of the DNA-histone complex to alter the tightness of chromatin's structure.
- This chromatin remodelling changes the accessibility of DNA to transcription factors, influencing gene expression.
- Changes may either compact genes (keeping them switched off) or make genes more accessible (keeping them switched on).
- This allows cells to control which genes are active, influence cell function, and respond to environmental signals.
Methods of epigenetic control and their effects on genes
DNA methylation and histone acetylation are examples of epigenetic modifications.
| Epigenetic process | Description | Effect on the molecule it modifies | Effect on chromatin | Effect on gene expression |
|---|---|---|---|---|
| Increased DNA methylation | Addition of methyl groups to DNA | Increases hydrophobic interactions, tightening DNA coiling | Condenses chromatin | Silences genes by preventing binding of proteins for transcription |
| Decreased histone acetylation (deacetylation) | Enzymatic removal of acetyl groups from histones | Increases histones' positive charge | Condenses chromatin | Silences genes by preventing binding of proteins for transcription |
Decreased DNA methylation or increased histone acetylation will have the opposite effect, making genes more accessible to transcription factors and increasing the rate of transcription.
Inheritance of epigenetic changes
Similarly to how DNA sequences can be inherited from a parent to their offspring, epigenetic patterns can also be inherited. This means environmental exposures can impact gene expression patterns in an individual and in their offspring.
Most epigenetic tags are erased during early development, but some may be passed from parent to offspring.
Examples of inherited epigenetic changes:
- Drought-induced epigenetic changes in plants can be transmitted to offspring to make them more drought resistant.
- Gestational diabetes can cause epigenetic changes in the fetus due to a greater exposure to glucose, increasing the likelihood of the child developing diabetes too.
Epigenetic defects and disease
Abnormal epigenetic regulation can result in altered gene function and diseases.
Examples of diseases caused by abnormal epigenetic regulation:
- In cancer, this often involves the silencing of tumour suppressor genes or the activation of oncogenes.
- Disorders like Angelman syndrome are linked to methylation defects.
Given that epigenetic defects are reversible, targeting these mechanisms with drugs offers a therapeutic option.
How drugs may counteract problematic epigenetic changes:
- DNA hypomethylating agents are used to counteract the silencing of genes caused by methylation in cancer.
- Inhibitor drugs that prevent histone deacetylation help to keep chromatin open, allowing gene expression.
A challenge remains in ensuring that epigenetic drugs specifically target only diseased cells.
The effect of RNA interference on gene expression
RNA interference is a process where small RNA molecules inhibit gene expression by destroying mRNA before translation.
This occurs as follows:
- Enzymes cut double-stranded RNA into small interfering RNA (siRNA).
- siRNA joins with enzymes.
- siRNA then guides the enzymes to specific sections of mRNA by pairing siRNA bases with complementary mRNA bases.
- The enzymes cut mRNA into several parts.
- mRNA can no longer be translated, inhibiting protein synthesis and thus gene expression.