Epigenetics – Putting the “epi” in epic

The latest craze in the world of science is to talk about epigenetics. You may have heard about it on TV or read about it in the newspapers, quite probably associated with some wonder cure or a way of shaking off those pounds without having to do anything.

Epigenetics is an extremely young area of interest in biology. It differs from good old-fashioned genetics in that it does not concern itself with the DNA sequence. Instead, it deals specifically with how chemical modifications made to the DNA and/or the proteins with which it associates (histones) can affect gene expression. It is an area of great interest because this regulation can have quite dramatic consequences, despite being relatively short-lived. These chemical modifications can be made and unmade very quickly, and thus ‘kick-in’ rapidly, yet can be triggered by simple changes in factors such as diet or exercise.

DNA is a long chain of individual molecules called nucleotides, which have three main parts: a deoxyribose sugar, a phosphate group and a base. There are four possible bases, which may be found in DNA (G, A, T or C) and certain sequences of these bases are used to encode proteins.

DNA molecules are enormous in length, as you might imagine given that they encode a human being. [Insert dubious statistic about length of DNA and distance to the Moon & back]. This presents a logistical challenge, because this information has to be readily accessible so that it can be read and copied to make proteins, yet it must also be stored away and protected within the small space of a cell’s nucleus.

The way in which nature has achieved this is by developing protein molecules around which the DNA can wind – the histones. Long chains of DNA wound around histone complexes coil and wind up even further, ultimately giving rise to the familiar ‘X’-shaped chromosomes that are seen during cell division (Figure 1).

The phosphate groups carried within the backbone of the DNA give it a strong negative charge. Figure 2 shows how the protein has many positively-charged ‘tails’ reaching out towards the coiled DNA. These opposite charges attract to keep the DNA tightly wound and stable. When the time comes that some of this DNA needs to be accessed to be read, there are enzymes that attach modifications (e.g. methyl groups –CH3) to the protein’s ‘tails’ to remove their positive charges. These modifications are completely reversible and provide flexibility in regulating which genes can be activated at a given time.

Methyl group modifications can also be attached to the bases within the DNA. This is yet another element of epigenetics and it works in a similar way to histone modification. These groups recruit proteins that block the DNA-reading machinery from accessing the DNA.

Why is this important?

This system adds a sophisticated level of control to gene expression and regulation. This is part of what allows us, as multicellular organisms, to exist. Breakdown of this control can lead to disease and has been shown to have an important role in cancer. Harnessing the power of the ‘epigenome’ is of intense medical interest for the development of new drugs and in the use of stem cells.

The importance of epigenetics is emblemised by the field of stem cell research. In the stem cells of the embryo all genes are accessible and there is very little epigenetic control. This is important because these cells will go on to differentiate and form all of the many varieties of cells in the body. Such stem cells, with the ability to become different cell types, are said to be ‘pluripotent’.  But, as these stem cells differentiate and become more specialised towards a particular task, the level of epigenetic control tightens, effectively closing off whole portions of the genome that are irrelevant for a particular cell type.

In 2012 Sir John Gurdon and Shinya Yamanaka won the Nobel Prize in Physiology and Medicine for their “discovery that mature cells can be reprogrammed to become pluripotent”. They found that the introduction of just four different proteins that help regulate gene expression (transcription factors) is sufficient for the reprogramming of a mature cell into a pluripotent stem cell. These transcription factors serve to wipe the epigenetic slate clean, and actually erase modifications at the epigenetic level to reopen the genome.

These cells can differentiate into any other cell type, meaning that it might, one day, be possible to generate replacement cells and tissues might to treat a huge range of medical conditions including heart disease and Alzheimer’s Disease.

This post, by author James Torpey, was kindly donated by the Scouse Science Alliance and the original text can be found here.

Reference:
http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/