What is epigenetics?

It's a question that I am often asked. The answer is complicated. Since, in my opinion, the viewpoint of the field shifts based on where the next sexy science that can generate money is coming from. 


So lets start with the word epigenetics and its semantic meaning. If we start by breaking down the word, we can see what the word and field has come to mean in the last twenty years. The first part epi is from Greek meaning above. Genetics....well realistically it is a galaxy of smaller fields dedicated to studying what genes are, how they are involved in disease and development, and how genes regulate each other. 

So epigenetics is the study of processes above genetics.........which is where the etiology fails to be useful. Hence the confusion amongst scientists and the public at large.


In a practical sense epigenetics is a in-depth look at how genes regulate each other. Genes are, at their strictest definition, the precursors to the proteins that perform (most of) the jobs that make life possible. 

While genes are the stars of the show, in terms of regulation of biological processes, they are the least interesting part of the genome. The interesting part is the so-called junk DNA or more accurately non-coding DNA. If genes are the stars, then non-coding DNA are the role players and the scenery that move the show forward. 


The dance of how these proteins and modifications is choregraphed is epigenetics. 


Non-coding DNA regions control which genes are expressed and when they are expressed. This occurs through RNA molecules, binding of proteins and enzymatic modification of these proteins. Its more complex that what I am highlighting but the core message here is that Epigenetics is about controlling access to the genome by RNA and proteins through the non-coding regions of genomic DNA. 


Epigenetic processes are the key to providing organisms the flexibility to respond to the environment. So what about these processes make them so important?  As with any regulatory process-it depends. 


The best analogy is the "genome as the book of life". If genes are the words by which an organism is "made" then epigenetics is everything else in the book. At the lowest level it is the sentence structure that allows the words to have meaning. At the highest level it is the chapter order that gives the story a linear order. Unlike a real book each tissue in the body can shuffle each of these elements on the fly....a choose your own adventure book based on cell type. Further flexibility arises from how each individual cell interprets the story that it is given.

While the book analogy is interesting and useful, the beauty of the system in my opinion is that all of this is managed through biochemistry: small differences in enzyme kinetics and subtle changes in protein binding. This biochemistry leads to a wide variety of markers that can be used to denote parts of the genome.


The cell uses different types of markers for each of the particular categories; grammar, pages, chapters. Each of the different markers that the cell can use for these categories has varying ease of use. The ease of use is a function of the biochemical processes by which the cell adds or remove the markers. If this all seems like overkill just to express a gene...it sort of is. Adding layers and differing ease of use allows the cell to add very tight regulatory control. This allows the cell to mix and match different markers to make bookmarks or highlight favorite passages, often used paragraph, etc.  

In general the chapter markers are direct methylation of the DNA. As the name suggests it is the addition (or subtraction) of methyl groups to DNA. This alters the affinity of DNA to a subset of proteins that occlude the DNA-basically hiding the genes. Removing the methyl groups abolishes this occlusion.

Sentence structure this is more complicated but in general there are 2 types of post translation modifications that are most commonly seen as having a definitive role in this process. This usually involves the structural proteins that surrond DNA. These proteins are the histones and they allow 2 linear metres of DNA to be packed a volume of 0.00001 metres. An amazing feat in and of itself!

Histones can be modified in a wide variety of ways too numerous to mention here. The combinatorial placement of these proteins and modifications on DNA allows for a very precise grammar to be used. So precise that cells can communicate exactly which protein should be expressed to their neighbor. Given that there may be as many as 31 thousand that is quite impressive. What are histones? that is another story for another post. The bottom line here is that these proteins control access to the DNA. The modifications on these proteins act to either loosen the structure and increase access or glue the proteins together blocking access.

So what you say? Well the answer is variation: variety in cells (brain VS muscle), variations between twins, variation in cell response, variety in drug response, variation in disease. Epigenetics is the root cause of variation at every level: species, organism, tissue, cells.

So until we understand how this biochemical signature is modified we can't really understand how cancers vary from person to person or in a bigger picture how we retain biodiversity. 

Health IT and clinical research

I recently returned from the E-Health Canada conference in Vancouver. I was there as an analyst for Info-Tech research group. I spoke about secure use of consumer devices in healthcare and the potential of cloud computing as a flexible model to deal with CoIT.


I was pleasantly surprised by the IT knowledge level of the nurses and doctors that attended the conference. Why was I surprised in this age of consumer devices and self service tech? Well I spend a fair amount of my time talking to and about IT departments. The impression that I get from many of them is that while most people can set up their email on their phone they remain largely clueless about the actual tech itself.  


Well, there is certainly a core of nurses and doctors that understand the tech and have really great ideas for how to make it work better in the context of healthcare delivery. I was left with the feeling that many remain frustrated with the current solutions and the pace that E-health is moving forward. The major areas of frustration were around content delivery and system upgrade for usability. I would summarize it as “You must do something; protect the data but be flexible on the device used”. Technology should allow doctors to spend more time looking and talking to patients not with their nose buried in a tablet. Just placing a tablet in the doctors’ hands doesn’t mean it will lead to increased use of the IT solutions for healthcare.


While some may point to this as a technology problem, it was clear from talking to the vendors that the solutions available today can meet the demands that hospitals are placing on IT. As someone with a past on the research and has dabbled in clinical research it was refreshing to know that there is a variety of solutions out there to make clinical research easier. What was interesting was how similar healthIT problems are to many other industries. In my opinion the issue is now about getting the best out of the tech not when will the tech exist.


 In other words its about getting the users and the admins on the same page. 


As someone with a deep passion about Rare diseases and use of high level biomedical research its somewhat frustrating that the system that is in use today is so antiquated. The upgrades available today could add so much intelligence to how we treat Rare diseases in particular. 


The new areas of stem cell therapy and epigenetics hold a HUGE promise if we can understand the relationship between disease and biology in these patients. Since they are so rare at any given location it is imperative that we have a way to share the data that is safe enough to share patient history across borders.