XMRV and epigenetics - a possible mechanism?

[ramakentesh]

I wonder if anyone has ever considered that other retroviruses are implicated in epigenetic changes to DNA.
In epigenetic changes the alterations do not change the gene itself but can either turn it off or alter its function.
So if a doctor looks at the gene it looks normal unless its methylation level is examined.
Its important to note that the methylation we are talking about here is quite different to the mechanisms mentioned by some CFS researchers.
The reason I mention it is that if XMRV is indeed implicated in tumour growth in the prostate, its likely that it plays a role in the hypermethylation of the promoters of tumour-supression genes.
Could it be that this retro-virus is - like the HIV does in many patients in relation to complications - is effecting the methylation of genes that regulate our autonomic and immune systems? It could explain the strange findings in CFS where the genes may appear normal.

Here many illnesses are examined in the context of pharm. side effects that may effect methylation:

http://www.novoseek.com/DocumentDet...MEDLINE&criterion=1&showType=5&docId=19501473

Abherant hypermethylation in prostate cancers:

http://www.ncbi.nlm.nih.gov/pubmed/14743506

And abherant hypermethylation as a result of another retrovirus HIV resulting in lymphomas:

http://www.newsrx.com/newsletters/Genomics-and-Genetics-Weekly/2003-12-12/1212200333349JW.html

And Im just touching the tip of the iceberg with this.


As an example, Postural Tachycardia Syndrome - which is often associated with CFS - is been connected with abherant hypermethylation of the NET gene promoter:

http://jop.sagepub.com/cgi/content/abstract/20/4_suppl/60

 

[ramakentesh]

And here, infection from H.Pylori induced hypermethylation and cancer:

http://www.ncc.go.jp/en/nccri/divisions/14carc/14carc03_1.html

 

[ramakentesh]

And - sorry to harp... From the Whittlemore website:


Research Team


Judy A. Mikovits, PhD, Director of Research [more...]


Dr. Mikovits spent more than 20 years at the National Cancer Institute in Frederick MD during which time she received her PhD in Biochemistry and Molecular Biology, investigating mechanisms by which retroviruses dysregulate the delicate balance of cytokines in the immune response. This work led to the discovery of the role aberrant DNA methylation plays in the pathogenesis of HIV

 

[cold_taste_of_tears]

What's an epigenetic mechanism, please?

A DNA cell that sits too close to a strobe light?
Ok, maybe not.....

Epi? Sigh, please explain wonderous brains of clan XAND!

 

[ramakentesh]

Its basically how the body regulates genes once we are alive - to promote certain traits and supress others in response to environmental stimuli. Why identical twins become more different as they age I think they also say.
As we age it appears our genes tend to become hypermethylated but it can happen earlier in gastritis, cancer and a few other illnesses but it has been implicated in a wide range of diseases.

 

[usedtobeperkytina]

Cfids

CFIDS Association has been saying for a while that the immune system genes do not act normally in CFS people. I forgot the exact term they used, cognitive problems.

Tina

 

[fds66]

Funny you should mention this because I was watching a two part programme here in the UK about identical twins and they were talking about epigenetics. I'd never heard of it but was about to do some research to see if anyone had looked at this in ME/CFS.

 

[ramakentesh]

But when they say that they dont act normally do they mean that they are functioning inproperly or that their actual transcription has changed?
Also why is it common for impaired acetylocholine blood flow responses and high norepinephrine in CFS?

 

[ramakentesh]

So far epigenetics has been the realm of cancer, but its implicated in weight gain/obesity, diabetes II, and many modern diseases as well as chronic gastritis. Because its a new area of study I guess it has been largely ignored by CFS researchers for reasons I am not sure.
There is one study on CFS and epigenetics that said there was hypermethylation of a gene that operated serotonin reuptake in some way but I cant find it when i searched today.
I guess the problem is that its hard to know where to look when there is conflicting evidence about what the primary problem is (adrenal axis, immuno disfunction, central nervous system/sympathetic overactivity, gluthione thingie, etc)

 

[Sing]

NOVA show on Epigenetics

I who never watch TV happened to turn one on and found a NOVA show (USA) on the discovery of epigenetics and its great importance. My poor memory tells me it started with a British researcher studying diabetes and obesity who looked at the family history, going back generations in a farming community, of times of starvation vs times of abundance. He found there were key, critical times such as before birth and puberty when certains genes were turned on or not. This then became a permanent change for that person, which was then passed down.

My vague sense of epigenetics is that there are the genes and then copies of the genes called epigenes which then become the operational part of the gene. The epigenes are the results of the genes meeting some environmental condition, adapting to it. The scary thing is that the epigenetic effects are passed down from one generation to the next.

However, some experiments were done in which some epigenetic effects were turned off, in laboratory animals, and the animal immediately went back to the original, normal gene's functioning.

I will try to find this show.

I think you are onto something in this thread!

Cecelia

 

[Sing]

NOVA show available on Epigenetics!

I found it! I googled NOVA and went to NOVA PBS.

Then to the right where the Health topic is listed.

Then scrolled down until I found the one on Epigenetics. There is a 17 min video. (I am sorry I don't know how to manage links!)

Cecelia

 

[_Kim_]

I found it! I googled NOVA and went to NOVA PBS.

Then to the right where the Health topic is listed.

Then scrolled down until I found the one on Epigenetics. There is a 17 min video. (I am sorry I don't know how to manage links!)

Cecelia

Hi Cecelia,

I found a 13 minute video on Epigenetics on the NOVA website. Is this the one you are referring to?

They have another section on epigenetics titled Ghost in Your Genes.

• Gene Switches focuses on epigenetic "switches" that turn genes "on" or "off."

• A Tale of Two Mice. A mouse gives birth to identical-twin sisters. One has brown fur and will grow up to be lean and healthy; the other has yellow fur and is destined to be obese and prone to disease. How can two mice sharing exactly the same DNA become so different?

I also found a 56 minute video Ghost in Your Genes - PBS Hawaii Epigenetics NOVA Episode

 

[nina_online]

So far epigenetics has been the realm of cancer, but its implicated in weight gain/obesity, diabetes II, and many modern diseases as well as chronic gastritis. Because its a new area of study I guess it has been largely ignored by CFS researchers for reasons I am not sure.
There is one study on CFS and epigenetics that said there was hypermethylation of a gene that operated serotonin reuptake in some way but I cant find it when i searched today.
I guess the problem is that its hard to know where to look when there is conflicting evidence about what the primary problem is (adrenal axis, immuno disfunction, central nervous system/sympathetic overactivity, gluthione thingie, etc)

I would be interested in reading about this study if you can find it.

Thanks,
Nina

 

[ramakentesh]

I believe the study is here in relation to CFS and epigenetics:

http://www.fasebj.org/cgi/content/meeting_abstract/23/1_MeetingAbstracts/LB202

This is a pretty complex example - often the CpG sites involved are purely on the promoter which when heavily methylated effectively turns the gene's transcription off.

Another interesting read on epigenetics and CFS is:

http://www.dreammanifesto.com/epigenetics-genie-genes.html

The exciting thought is that there are medications already in existence that can demethylate genes and turn their transcription back on:

http://en.wikipedia.org/wiki/Demethylating_agent
http://cancerres.aacrjournals.org/cgi/content/abstract/63/16/4984

and in feverfew:

http://jpet.aspetjournals.org/content/329/2/505.abstract

Although the main agents are decitabine and 5-azacytidine.


And here are examples of things like infections and even medications that may result in epigenetic changes that are permanent:

http://www.ncbi.nlm.nih.gov/pubmed/19639175

http://www.novoseek.com/DocumentDetailActi...;docId=19501473

 

[fresh_eyes]

Hi ramakentesh, thanks for this interesting topic. Maybe the answer to this question is in the links you posted, but I'm afraid I don't have the brainpower right now to read them all. We had a discussion going about studies looking at the way XMRV (and other viruses) may induce transcription of some of the endogenous retroviruses that make up 8% of the human genome. Would this fall within the field of "epigenetics", or does the term just apply to - well, I don't know how to describe them, I'll just say "regular genes"?

 

[Sing]

Thank you so much Kim for fielding the ball so well, finding those links to NOVA videos on epigenetics. Fresh_Eyes, maybe those would be an easier place to start to understand? I want to look at your links too, Ramakentesh, to see if I can follow the information. It is a hopeful realm of study and possible treatment!

Cecelia