Biology

Epigenetics

By Mansi Chitnis

Epigenetics can be defined as the study of gene expression, and phenotype, without altering the DNA sequence (1). DNA modifications, such as the addition of a methyl group, can affect whether the gene is ‘switched off’ or to be expressed (2).

All cells begin as an undifferentiated stem cell, resulting from the fusion of an egg cell and a sperm cell. This rapidly divides to form a blastocyst of totipotent and pluripotent cells which have the ability to differentiate into the specific cells that humans are comprised of. This process of differentiation was compared eloquently by Conrad Waddington to a marble rolling down a hill. At the top, the marble represents the stem cell, whereas at the bottom the marble represents a functional specialised cell, such as a nerve cell. This model is known as Waddington’s epigenetic landscape and can be seen in the diagram below. (1)

Conrad Waddington’s Epigenetic Landscape (3)

Two theories were proposed with regards to the way in which a stem cell was able to differentiate, and therefore express different proteins. The initial stem cell must contain all the DNA which codes for the organism so as it differentiates it must either permanently ‘switch off’ sections of DNA or lose the unnecessary sections of DNA (2). John Gurdon’s experimental nucleus transfer suggested evidence for the cells being able to switch off sections of DNA which code for the unnecessary proteins. He was able to successfully transfer an adult toad nucleus from a somatic cell into an enucleated egg cell, which produced normal tadpoles (2). This experiment suggested that somatic cells retain their pluripotency. Therefore, there must be a mechanism which stops the expression of sections of DNA without altering the genetic code itself (2).

The most well-known epigenetic modification is the addition of a methyl group to the DNA. The addition of a methyl group prevents DNA expression. Methyl groups are added to sections of DNA with a CpG group – a cytosine nucleotide followed by a guanine nucleotide. Similarly, there must be an epigenetic alteration that promotes DNA gene expression – histone modification (2). There are a wide range of other modifications that are being constantly discovered, adding to our understanding of the relationship between epigenetics and various genetic diseases (1).

What does this mean for human health? Data from the Dutch famine of 1944 and 1945 has demonstrated a strong link between environmental influences on gene expression. Those exposed to the famine were demonstrated to have less methylated insulin growth factor II genes, and thus, increased rates of coronary heart disease (1). Epigenetic research also has implications for the treatment of previously incurable disease. In 2007, Professor Adrian Bird published research claiming to have cured Rett Syndrome in rats. Rett Syndrome is a result of a mutation is the MeCP2 gene which codes for a protein that recognises DNA methylation. This means although the DNA is correctly methylated, this methylation cannot be read. Adrian Bird was therefore able to demonstrate in rats that if an inactivated MeCP2 gene was switched on later on in the rat’s life, it no longer expressed symptoms of Rett Syndrome. This research is defining in the sense that is able to show potential for treatments of complex neurological diseases that were previously thought to be incurable (2).

Following this research, there have been many attempts, successful and unsuccessful, in showing the relationship between epigenetics and human diseases. The potential of this research has been immense and we can conclude that there is still hope that one day in the future many diseases which are now a death sentence will be curable.