‘’These patterns of gene expression are governed by the cellular material — the epigenome — that sits on top of the genome, just outside it (hence the prefix epi-, which means above). It is these epigenetic "marks" that tell your genes to switch on or off, to speak loudly or whisper. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next.’’
Time Magazine (2010) The quote above may well be a few years old now, but its importance is abundantly obvious. Although, three years may have passed since that issue of Time magazine was distributed, a great deal of people have still never heard of epigenetics and those that have know very little of its workings. Its hard to express the impact that epigenetics has had and has the potential to have on modern molecular genetics. Just over twelve years ago when the Human Genome Project results were released, a great deal of people though that the definitive answers to fundamental questions would be unearthed . However, this was not the case and the results told us very little and actually produced more questions than answers. How were these genes regulated? What factors affected gene expression? Dynamic regulation? All of these questions culminated in the launch of the ‘ENCODE’ (Encyclopedia of DNA elements) project in September 2003. A project that was designed to assess epigenetic features that act to control the expression of our genome. The results were published in September of last year (2012) and the reaction was of pure astonishment . For example, we know now that 80% of our genome is transcribed (the transcriptome) and is functional, yet only 2% of that is translated .
Whilst that quote stationed at the top of the page summarizes epigenetics quite succinctly, there is a great deal more to the subject than that. In previous posts, I have discussed genetic mutations and the trouble we have in even defining a gene. I suppose this post focuses on the regulation of genetic expression. We have all of these genes in every cell, how do are cells know which genes to express and conversely which to suppress; it seems the answer lies in epigenetics . Also, many researchers find that these epigenetic mechanisms that regulate gene expression are dynamic and can change (even within generations). So, when an environment is responsible for a phenotypic change it is normally due to the fact that the epigenetic mechanisms have reacted to the change and altered the genetic expression (epigenotype I suppose?) of the organism .
I should probably make it clear that epigenetic ‘phenomena’ or changes are understood to a very good level and normally focus on the change of DNA structure. For example, it is clear to see that tightly packed DNA is less likely to be transcribed than loosely packed DNA (this ‘DNA’ is normally referred to as chromatin as it is associated with packing proteins such as histones). Epigenetics act by changing this level of chromatin packing from tight to loose and vice versa; thus influencing which parts of the genome are transcribed. I shall discuss three ways in which epigenetic changes influence the expression of our genome. I shall introduce the methylation of DNA (adding a CH3 group), the acetylation of histones (adding an acetyl group to the histone proteins that pack DNA) and finally the impact of chromatin remodeling complexes.
Epigenetic MechanismsThe DNA in an average cell is highly packaged simply to allow it to fit inside the cell. I won’t delve into the packaging problem fully, but to understand the following mechanisms of epigenetic change it is important to understand chromatin packing to a certain extent. DNA is coiled into a thread-like state; this thread is then wound around disc-like packing proteins called histones to form a structure that looks similar to beads on a string . There is further packing and super-coiling, but here it is important to imagine the DNA packed into a formation that looks similar to beads on a string . Notably, the ‘beads’ in this case are called nucleosomes (a combination of a histone protein and the DNA wrapped around it) whilst the ‘string’ between the ‘beads is called linker DNA; the whole ‘string of beads’ is termed chromatin . Also of note, chromatin is generalized into either heterochromatin that is tightly packed and rarely transcribed or euchromatin that is loosely packed and highly transcribed .
Epigenetic mechanisms can affect whether a certain piece of DNA is packed into heterochromatin or euchromatin and this can affect the transcription potential of certain genes. The DNA can be methylated (methylation occurs at CpG base repeats) causing the DNA to be tightly packed and rarely transcribed. So, if a gene needs to be turned off then it is normally methylated . Conversely, the histone proteins that the DNA wraps around can be acetylated leading to loosely packed chromatin structure (euchromatin) . This acetylation of histones causes their interactions with the DNA to be reduced meaning the DNA can be accessed by transcription machinery. Finally, there exist such things as ‘histone remodeling complexes’ that act to move the histones along the DNA, effectively moving the position of the nucleosome and allowing new accessible linker DNA to be formed. Thus, altering the DNA that is transcribed and consequently the genes that are expressed .
Impacts, Current Research & The FutureSo, we have sequenced the human genome, we know where the genes are and now we know hoe the changes in the structure of the chromatin effect how these genes are expressed. But what does this allow us to understand?
Well, the impacts of this research have really yet to be seen in full. Obviously, as epigenetics regulates gene expression it has impacts in developmental biology regarding cell differentiation. For example, studies have been conducted that link epigenetic phenomena and the time of female puberty . Moreover, epigenetic changes are related to many human diseases; particularly cancers. Epigenetics regulates the transcription of DNA and consequently protein synthesis generating an obvious connection with cancer (uncontrolled cell growth) as when certain suppressive epigenetic alterations are not employed cancer may result . The ENCODE results have and will continue to be an invaluable reference with regards to conducting this research successfully. In my opinion, knowing how the expression of the genetic code is regulated is equally, if not more important than the sequence of the code itself.
I believe it is more than fair to say that epigenetics is the future of modern genetics, we know the code, but unlocking how that code is utilized within cells in of paramount importance. Research in epigenetics will allow us to understand cell differentiation to an even greater extent and possibly allow us to develop a greater understanding of various diseases. The epigenetic quest is still in its infancy, but its maturity will be of great interest not only to geneticists or scientists but also to every human on the planet. May be at some point in the near future we will know exactly how genes are turned on and off, how different cells develop and how diseases result from the malfunction of these processes, but until then our genes continue to baffle us.
PLEASE NOTE- This article and more are available WITH references via the link below:http://biochemperspectives.blogspot.co.uk/
