Epigenetics: Around the Twist



Gerald Clarke
05/13/2013

The old argument of nature vs nurture has been known to be a false dilemma for a long time, the true making of an organism lies in both and no topic illustrates this better than epigenetics. Epigenetics; a word which will catch the attention of any biologist, a blossoming field with gripping case studies involving Nazis and hardship, it is unquestionably one of the hottest topics in genetics today. One of the peculiarities for a topic with such widespread attention is that the definition is still a contentious topic. For our purposes, we will use the definition ‘the control of gene expression not involving a change in the DNA sequence’.

Dutch Famine 1944

During the later days of the Second World War, the Dutch people’s refusal to collaborate with Nazi forces was met with a harsh punishment; the embargo of food goods to the western Netherlands. A cold winter which devastated crops and the war-decimated infrastructure meant that the populace had very little of their own food and sparse access to getting food shipped in. From September 1944 the people began to starve and at least 18,000 people died. The harsh conditions were not totally lifted until the liberation of the western Netherlands in May 1945.

Cohort Study

This tragic tale of bravery, callousness and logistics may have been a truly senseless episode in a tumultuous time in world history, but it has provided us with a rich scientific legacy which has given us important insights into how life operates. The Dutch Famine Birth Cohort Study was a long term scientific observation of those people who lived through the famine, monitoring not only their health, but also that of their children and grandchildren to analyse the long term effects of malnutrition. The effects on babies who were exposed to famine in utero were many and varied including effects on birth weight and risk factors for coronary heart disease and diabetes. The extent of these effects depended on when in the pregnancy that exposure happened. The most amazing thing about these effects is that some have been demonstrated to be transgenerational i.e. babies with smaller than average birth weights also grew up to have babies who had smaller than average birth weights. The nutrition of these people’s grandmothers was affecting their health decades later!

Mechanism

Two of the main routes through which these epigenetic effects take hold are DNA and histone modification. DNA methylation is the addition of a small chemical group to the DNA, these groups affect the protein machinery which is involved in the transcription of the genetic code. In the cell, DNA is wound around proteins called histones like a thread wound once around a spool. These histones are responsible for numerous functions in cells one of which is controlling the physical accessibility of DNA. Methylation of histones can be associated with either active or silenced DNA depending on which amino acid is methylated. These markers were originally thought to be wiped clean before the cell divides, however it has now been demonstrated that not all of them are and so this epigenetic information can pass from cell to cell or generation to generation. Eventually all of them will be removed; however epigenetic effects have been shown to pass through 2 generations.

Disease and Treatment

Unsurprisingly, this powerful mechanism has been shown to play a role in disease. Cancerous cells can silence the protective tumour suppressor genes or activate the cancer promoting oncogenes. Epigenetics has been shown to play a role in developmental disorders and disorders of mental retardation such as Rett syndrome, Angelman Syndrome and Fragile X. Understandably, with their wide role in many cellular mechanisms epigenetic pathways are seen as a rich seam in which to prospect for drug treatments, for example the proteins responsible for DNA methylation are currently being investigated by drug companies as targets for cancer treatment.

This is only the beginning; biology has undergone revolution after revolution, consistently changing the scientific landscape to create better and better models for how life works. Epigenetics is a nascent field and it is likely that many more revolutions are on their way.

What do you think the most promising developments in epigenetics are? How do you think this will affect the pharma industry? Let us know in the comments below.