1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Can You Come for a Visit? My ME/CFS Says No
My daughter and son-in-law just had a baby last week. We are thrilled. But we won't be able to see the baby or hold her any time soon. We won't be able to take over little gifts or help out with housework or babysitting.
Discuss the article on the Forums.

Xmrv this is what frightenes me

Discussion in 'XMRV Research and Replication Studies' started by Gerwyn, May 22, 2010.

  1. Gerwyn

    Gerwyn Guest

    THIS FOLLOWING SECTION DESCRIBES THE ROLE OF RETROVIRUSES IN CREATING ONE OF OUR MASTER REGULATORY GENES.IT IS IN LAY LANGUAGE.THROUGHOUT THE READING BEAR IN MIND THAT XMRV HAS BEEN FOUND INSERTED INTO CREB__A MAJOR REGULATING GENE IN ITS OWN RIGHT
    THERE IS A STING IN THE TALE(not a typo for a change!)

    Scientists have long suspected that retroviral elements could play a role in gene regulation. More than 50 years ago, Nobel Laureate Barbara McClintock observed that transposable elements--or "jumping genes"--altered gene expression in maize. In 1971, Roy Britten and Eric Davidson theorized that commonly observed repetitive DNA sequences actually served as codes for gene regulatory networks. The DNA remnants of retroviruses tend to be repetitive sequences and can jump around, when active.

    The UCSC team finally gathered concrete evidence to support Britten and Davidson's hypothesis. The group trolled the human genome for ERVs, identified p53 binding sites in them, and tested their ability to activate genes regulated by p53. More than one-third of all known p53-binding sites turned out to be associated with ERVs, they discovered.

    These results raise new questions about the role of so-called "junk DNA," the vast regions of the genome that don't code for proteins. ERVs fall into that category. Many scientists once believed that such DNA served no purpose, but new data from the Haussler lab and other labs are challenging that view.

    "We're starting to uncover the treasure in this junk," said Wang.

    Moreover, the team has proposed a new mechanism for evolutionary change. Conventional wisdom says that evolution is driven by small changes--point mutations--to the genetic code. If a change is beneficial, the mutation is passed onto future generations.

    Now it appears that another level of evolution occurs that is not driven by point mutations. Instead, retroviruses insert DNA sequences and rearrange the genome, which leads to changes in gene regulation and expression. If such a change in gene regulation is beneficial, it is passed onto future generations.

    This research should have broad implications, according to Wang.

    "Our prediction is that this is a general mechanism that has been around ever since viruses," Wang said. "ERV-mediated expansion of a gene regulatory network probably happened more than once and not just in primates. We predict it led to other master gene regulators, not just p53."

    Mol Cell Biol. 2000 July; 20(13): 48494858.

    PMCID: PMC85936
    Copyright 2000, American Society for Microbiology
    p53 Recruitment of CREB Binding Protein Mediated through Phosphorylated CREB: a Novel Pathway of Tumor Suppressor Regulation
    Holli A. Giebler, Isabelle Lemasson, and Jennifer K. Nyborg*
    Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870

    If XMRV affects the function of creb by creating polymorphic proteins due to insertional mutagenesis
    (Silverman et al) then our master gene regulate would not have the same ability to regulate creating a snowball effect
  2. flybro

    flybro Senior Member

    Messages:
    581
    Likes:
    5
    pluto
    This may be a dopey question,

    I think I remeber Klimas saying she wanted to do an exercise study to see wich genes 'on of', switches changed.

    does ths mean that our on off genetic switches can be different at different times.

    and would Klimas be on track with her line of thinking with the test she wants to do, consdirei9ng this
    sorry my science education focused on domestic engineering LOL.
  3. awol

    awol *****

    Messages:
    417
    Likes:
    0
    Thanks Gerwyn. This clarifies some of the points you have been making very well. I agree, scary.
  4. Gerwyn

    Gerwyn Guest

  5. CBS

    CBS Senior Member

    Messages:
    1,364
    Likes:
    246
    Western US
    I'm very interested in seeing what Drs. Light, Light, Singh and Bateman come up with as they have already tested the Light "exercise subjects" for XMRV. The distinct genetic expression in CFS patients post exercise was striking. Correlating genetic up and down regulation with XMRV status could be huge.
  6. Dr. Yes

    Dr. Yes Shame on You

    Messages:
    867
    Likes:
    22
    Hey G,

    Could you get me the references for the first point (XMRV found inserted into CREB), and for the second (insertional mutagenesis by XMRV)? When and IF yer up to it of course!

    I thought the last paper I saw co-authored by Silverman (Kim et al, incl. Silverman 2010, about fidelity of site integration by XMRV) found high fidelity integration by XMRV (i.e. very low probability of insertional mutagenesis, relative to other retroviruses), though they still noted the importance of looking further into the issue.
  7. parvofighter

    parvofighter Senior Member

    Messages:
    436
    Likes:
    99
    Canada
    Shedding Light on gene regulation

    Indeed CBS, I totally agree. Wouldn't correlating genetic regulation with XMRV status, in effect deep-six the psycholobby's entire premise re: ME/CBT/GET? Now these upcoming results ARE something I'd love to hear Fiona Godlee "independently" comment on.

    Addendum: When I completed my Masters, I inadvertently blew a hole in the class ceiling with the cork from a magnum of champagne I had smuggled onto campus (unbeknowst to me, it had rolled around a tad in the trunk of my car on my way to uni, that morning:Retro redface:). But the explosion and ensuing damage were spectacular, and an entirely fitting end to 2 gruelling years. And the janitors were very kind about it.

    My aversion to champagne notwithstanding, I may just have to invest in some bubbly when Bateman and Singh's latest ME/CFS/XMRV research comes to Light.:Retro smile:
  8. natasa778

    natasa778 Senior Member

    Messages:
    1,409
    Likes:
    1,208
    London UK
    Is anyone in touch with those guys? if so, pass this on please - it is a very very new technique that enables looking at CREB activity in living cells. The probably are well aware but it would not hurt to ask :)

    J Biol Chem. 2010 May 18. [Epub ahead of print]

    Imaging CREB activation in living cells.

    Friedrich MW, Aramuni G, Mank M, Mackinnon JA, Griesbeck O.
    Max-Planck-Institute of Neurobiology, Germany.

    The Ca 2+- and cyclic adenosine monophosphate responsive element-binding
    protein CREB and the related ATF-1 and CREM are stimulus-inducible
    transcription factors that link certain forms of cellular activity to
    changes in gene expression. They are attributed to complex integrative
    activation characteristics, but current biochemical technology does not
    allow dynamic imaging of CREB activation in single cells. Using
    fluorescence resonance energy transfer between mutants of GFP we here
    develop a signal-optimized genetically encoded indicator that enables
    imaging activation of CREB due to phosphorylation of the critical serine
    133. The indicator of CREB activation due to phosphorylation (ICAP) was
    used to investigate the role of the scaffold and anchoring protein
    AKAP79/150 in regulating signal pathways converging on CREB. We show
    that disruption of AKAP79/150 mediated PKA anchoring or knock-down of
    AKAP150 dramatically reduces the ability of PKA to activate CREB. In
    contrast, AKAP79/150 regulation of CREB via L-type channels may only
    have minor importance. ICAP allows dynamic and reversible imaging in
    living cells and may become useful in studying molecular components and
    cell-type specificity of activity-dependent gene expression.
    PMID: 20484048
  9. Mithriel

    Mithriel Senior Member

    Messages:
    564
    Likes:
    40
    Scotland
    My breath is taken away every time I am reminded that our so called "lunatic fringe" is wanting biomedical experiments done, like examining gene mutagenesis in CREB, while "mainstream medicine" is getting money to run a study into the lightening process in children.

    And for this we are mocked by self styled quackbusters.

    Mithriel
  10. V99

    V99 *****

    Messages:
    1,471
    Likes:
    1
    UK
    What Mithriel said
  11. awol

    awol *****

    Messages:
    417
    Likes:
    0
    just goes to show that psychiatrists are often the ones in the most need of psychiatric help!
  12. Gerwyn

    Gerwyn Guest

    I think that the silverman paper actually mentioned insertion into creb and NFAT.The first time it was not.if memory serves me right it was Urlisman.The integration of xmrv is caused by the process of insertional mutagenesis.The fidelity of integration is the problem!.
  13. Dr. Yes

    Dr. Yes Shame on You

    Messages:
    867
    Likes:
    22
    Sorry G, I meant deletion, etc mutations due to sloppy site integration, not "clean" insertional mutagenesis. I re-checked the Kim 2010 paper (w/ Silverman), and they did find that site integration for XMRV is high fidelity. However, they caution that:
    Still, if the 2010 paper's findings hold true for all XMRV integration sites, then fidelity of site integration wouldn't be the problem but rather the site selection by XMRV and the disruptive presence of its sequence alone. In that case pathology would be caused by over or under expression of the gene, especially if the insertion is in a promoter sequence.

    [Btw, found the reference for integration into CREB and NFAT - Dong et al (incl Silverman) 2006.]
  14. Gerwyn

    Gerwyn Guest

    yep very much site selection !

See more popular forum discussions.

Share This Page