Altering Gene Expression

[Second_Amendment]

Since it’s been confirmed PFS is a case of silenced genes, I think we should focus our PFS studies and discussion around this topic and not candida, autoimmunity, or chronic prostatitis.

I came across an interesting article (review of an article actually) that has identified a protein that might be of interest to awor’s team. This protein is JHDM2A.

This new study identified a protein that can demethylate the histones that are associated genes important in prostate cancer, and reactivate gene exp the new protein plays a role in gene activation mediated by androgen receptor, a protein that responds to androgen hormones.ression from those genes. The important point is that up until recently, it was thought that these histone modifications were permanent and the associated genes, once silenced, couldn’t be reactivated. This newly described protein allows those genes to be reactivated.

…

For the second time in less than a year, University of North Carolina at Chapel Hill scientists have purified a novel protein and have shown it can alter gene activity by reversing a molecular modification previously thought permanent. The findings, published in the journal Cell, also show that In this regard, the novel protein may figure in the development of prostate cancer. Androgens, particularly testosterone and dihydrotestosterone, determine male secondary sex characteristics and stimulate prostate cell growth.

fpwr.org/blog/research/altergeneexpression

The Cell paper

Covalent modification of histones plays an important role in regulating chromatin dynamics and transcription. Histone methylation was thought to be an irreversible modification until recently. Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. Similar to JHDM1, JHDM2A-mediated histone demethylation requires cofactors Fe(II) and α-ketoglutarate. Mutational studies indicate that a JmjC domain and a zinc finger present in JHDM2A are required for its enzymatic activity. Overexpression of JHDM2A greatly reduced the H3K9 methylation level in vivo. Knockdown of JHDM2A results in an increase in the dimethyl-K9 levels at the promoter region of a subset of genes concomitant with decrease in their expression. Finally, JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.

Almost certainly a protein of interest for awor’s team.

cell.com/abstract/S0092-8674(0600385-0

[Mew]

Since it’s been confirmed PFS is a case of silenced genes,

I don’t think anything has been confirmed 100% yet as to exact mechanism, only strong evidence pointing in certain/specific directions. Once a paper is published we will have a better idea of specifics. However, as Awor is in touch with the research teams, I’ll defer to his viewpoints on this.

[tim1911]

You are aware this thread exists?

viewtopic.php?f=27&t=412

Change in gene expression 2007

[Second_Amendment]

I think the question we should be asking ourselves is what epigenetic effect has taken place? DNA methylation, histone deacetylation, or some type of chromatin modification? I know this is a complex subject and it is not all-or-nothing. But I think looking at the success rates of some drugs might help shed some light. The unusally high success rate with HDAC inhibitors (antibiotics, dexamethasone, GHB) hints at some type of histone deacetylation. As far as I know, awor is the only person to try a demethyation agent. He had some initial succes with that but it didn’t last coming off anti-depressants and didn’t want to risk side effect with further treatment. Big Softie’s success with resveratrol was more likely due to its anti-cancer properties than its testosterone raising abilities. Resveratrol has demethylation properties: hal.archives-ouvertes.fr/docs/00/37/62/82/PDF/Curr_Drug_targ06.pdf

We need some more guinea pigs.

[spstriken]

has you SA found more success stories with Resveratrol?