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).

Figure 1. Zooming out from DNA (1), to DNA wrapped around histones (2), through to an entire X-shaped chromosome formed from lots of DNA wrapped around lots of histones (5). Image source: Wikimedia Commons (Author: Magnus Manske). Image used under Creative Commons License 3.0)
Figure 1. Zooming out from DNA (1), to DNA wrapped around histones (2), through to an entire X-shaped chromosome formed from lots of DNA wrapped around lots of histones (5). Image source: Wikimedia Commons (Author: Magnus Manske). Image used under Creative Commons License 3.0)
 Figure 2. DNA wrapped around a histone (Image source: Wikipedia (Author: PDBot). Image used under Creative Commons License 3.0)
Figure 2. DNA wrapped around a histone (Image source: Wikipedia (Author: PDBot). Image used under Creative Commons License 3.0)

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/

7 thoughts on “Epigenetics – Putting the “epi” in epic

  1. That’s really quite amazing. I was not familiar with the word ‘epigenetic’ but this sounds like it would have huge medical implications in the future. Thank you for explaining it.

  2. That is quite ‘epic’! It would be amazing to find a cure for Alzheimers. I think it is terrible not to be able to remember anything…what’s the use of all the memories you made your whole life if you can’t enjoy them later in life. If these cells are able to differentiate into any type of cell, there is hope for people that are paralysed to be fully functional again oneday. AMAZING!

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  3. As fascinating as it might sound, manipulating the genetic make-up of an organism might backfire at an unprecedented level. Deliberate alterations to genetic sequences might actually cause gene mutations or uncontrollable tumors at an astounding pace or fix a problem and simultaneously create another or wouldn’t this lead to more genetic or even chromosomal complications? If more research, effort and time is put into it, this can be the most EPIC approach to almost every genetic disease that is on earth.

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  4. This research is really amazing!! I was also not familiar with that term epigenetics but now i am.I think this research will really benefit the medical field and also will benefit those suffering with heart disease and Alzheimer ,and finally this research can help scientist to come up with other cures like cancer.

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  5. These are great news, this technique can, by surprise also assist in treating autism spectrum disorder. It’s really good to know that scientists, researchers, medical doctors etc are fighting for other people’s lives. It is very vital to invest in education and research as the key to all incurables is right in front of our eyes.

  6. This is interesting and because epigenetics has the ability to cure/treat diseases like the heart disease but because this has to do with manipulating the human genes consequences of such things should be looked at.

    “Harnessing the power of the ‘epigenome’ is of intense medical interest for the development of new drugs and in the use of stem cells” this then should that if it is researched more and it is found to be effective without any serious damages to the human genes it could be the answer to many diseases.

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