Wednesday, 16 May 2012

DNA methylation: a new approach to modifying cancerous & other diseased cells.


DNA methylation: a new approach to modifying cancerous & other diseased cells.

Epigenetics is a fairly new area of genetics, epi- is a Greek prefix meaning above, on or over and epigenetics refers to the study of gene expression other than that of a specific change in the nucleotide sequencing. DNA methylation is a form of epigenetic signature, it is fairly common throughout DNA and is more closely related to cell identity, which is what it sounds like; how’s cells identify themselves. Or for example; how a skin cell, knows not need to produce insulin, while a pancreatic cell knows that it shouldn’t produce pigment. (Health Canal 2012) I won’t dive too deep into the specifics but basically; a methyl group is attached to specific CG sites in the DNA sequence. This is where Cytosine and Guanine are sitting side by side, within DNA. A research paper was published earlier this month in the scientific journal Cell Metabolism titled “Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle”, the subject of the study being how exercise induces instantaneous methylation changes, subsequently altering gene activity to better burn lipids and carbohydrates within mitochondrial function. The research recruited fourteen young and healthy recruits who were punished on an ergometer for incremental short bursts of exercise – fun. Immediately after the pain, more pain was administered in the form of a muscle biopsy which was taken and the methylation then tested. Another biopsy was taken twenty minutes later to examine the difference in methylation levels, and what do you know, they discovered “that acute exercise induces gene-specific DNA hypomethylation in human skeletal muscle.” (Barrès et al. 2012)
Figure A shows the change in methylation, whereas figure B shows the ratio between the levels of methylation on specific genes.
Barrès and co. believed they made a pretty significant discovery, seeing as epigenetics when it first came about wasn’t seen as an important player in the game of genetics. But what they discovered is that hypomethylation is occurring all the time within our DNA, so it’s not as stable a process as once was believed. Their hopes with this is that this can remove some of the fear around tampering with methylation levels within DNA. In other scientist’s defence, this is a fair call as a methylation imbalance has been linked tumour progression (Baylin et al. 1998).
So how does this mean that we can modify cancerous and other diseased cells? Well Barrès believes that they “have shown, that just by exercising, you, yourself manipulate the DNA of your cells. Our DNA is not as stable and unchangeable as previously thought.” (Health Canal 2012). As I said earlier, cell identity and gene expression has much to do with methylation, so how about telling different cells to heal themselves? Or seeing as the original discovery was in fact to do with methylation caused by exercise, what I we could tell cells that they were exercising when they were performing little or no exercise? I can imagine international pharmaceutical giants salivating at this thought – but it could be put to much better use to by simulating exercise for diabetics who have lost both legs to their diabetes. Or perhaps people with severe depression – exercise and fitness is known to improve the symptoms within these people.
Barrès and co. have hungry eyes at this stage and feel that they have opened the door to a whole avenue of new research, but it is very early days so you shouldn’t be getting too excited about that ‘diet pill’ just yet.

References:
Barrès, R, Yan, J, Egan, B, Treebak, JT, Rasmussen, M, Fritz, T, Caidahl, K, Krook, A, O'Gorman, DJ, & Zierath, JR 2012, ‘Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle’, Cell Metabolism, vol. 15, issue 3, pp. 405-411.
Baylin, SB, Herman, JG, Graff, JR, Vertino, PM & Issa, JP 1998, ‘Alterations in DNA methylation: a fundamental aspect of neoplasia.’, Advance Cancer Research, vol 72, pp. 141-196.
Health Canal 2012, Exercise changes the genetic identity of your muscle cells, viewed 12 March 2012, <http://www.healthcanal.com/genetics-birth-defects/27271-Exercise-changes-the-genetic-identity-your-muscle-cells.html>.

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