What is the epigenome?

Derived from the Greek “epi” meaning “above”, the epigenome describes modifications to the genome that do not affect the DNA sequence but determine whether genes are switched on or off where and when they are needed.

If the genome is analogous to the script of a play, the epigenome is the interpretation of the play by the director and actors.

Two components of the epigenome are DNA modification and chromatin remodelling. DNA modification describes the addition of chemical compounds to the DNA bases. Methylation of DNA is the commonest modification. Methylation at the start of a gene usually switches the gene off. Chromatin remodeling describes how changes to the structure of DNA can affect gene expression. As you will remember from previous steps, the DNA is wound around histones in order that it can be packaged efficiently into the nucleus as chromosomes. Gene expression can depend on how tightly the DNA is bound to the histones: when it is loosely bound genes are accessible to transcription factors and can be expressed but if it is tightly bound transcription can not occur. The tightness of the histone / DNA binding is determined by chemical modifications (again methylation amongst others) that occur to “tails” that protrude from the histone molecule.

Chromatin remodeling © St George’s, University of London

The epigenome is dynamic and responsive to external stimuli. It is believed that certain external stimuli can cause abnormal DNA modifications which, in turn, disrupts normal gene expression. For instance, we now know that a defective epigenome can contribute, along with genomic mutations to the development of cancer.

A different group of disorders that arise from abnormalities of the epigenome are the imprinting disorders. Imprinting is an epigenomic phenomenon whereby certain genes are expressed depending upon their parent-of-origin, i.e. whether a gene is “switched on” or “switched off” depends on whether it was inherited from your mother or your father. In certain regions of the genome, there is clustering of imprinted genes which are regulated by imprinting control centres. Abnormal imprinting patterns are responsible for a few rare disorders including (amongst others) Beckwith Wiedemann syndrome (increased tongue size, abdominal wall defects, ear lobe creases / pits and an increased predisposition to developing certain childhood tumours); Prader Willi syndrome (intellectual disability, obesity and hyperphagia) and Angelman syndrome (intellectual disability, seizures and characteristic facial appearance).

Epigenomics is a growing field and one, about which, we still know relatively little. However, the study of the epigenome is a rapidly expanding area and, like our burgeoning knowledge of the genome, our increasing ability to interpret the epigenome is likely to transform our ability to both diagnose and treat rare and common disease.

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The Genomics Era: the Future of Genetics in Medicine

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