Lysine-Specific Demethylase 1 (LSD1)

Science Other Studies
#1

Also posted this in the thread “Reversing silenced AR signal with demethylating agents - A promising treatment option?” link>http://www.propeciahelp.com/forum/viewtopic.php?f=5&t=3901&p=30415#p30415

Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression.

Posttranslational modifications of histones, such as methylation, regulate chromatin structure and gene expression. Recently, lysine-specific demethylase 1 (LSD1), the first histone demethylase, was identified. LSD1 interacts with the androgen receptor and promotes androgen-dependent transcription of target genes by ligand-induced demethylation of mono- and dimethylated histone H3 at Lys 9 (H3K9) only.

ncbi.nlm.nih.gov/pubmed/17277772

LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription.

LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9 (H3-K9), thereby leading to de-repression of androgen receptor target genes…Thus, modulation of LSD1 activity offers a new strategy to regulate androgen receptor functions. Here, we link demethylation of a repressive histone mark with androgen-receptor-dependent gene activation, thus providing a mechanism by which demethylases control specific gene expression.

ncbi.nlm.nih.gov/pubmed/16079795

#2

Nice find. I wonder if Awor and his doctors are aware of this.

#3

This could be very important, IF methylation is the problem.

Awor mentions this paper[1] to support his use of procaine to demethylate, however it doesnt actually mention androgen receptors. It mentions procaine to demethylate where there is an addition of methyl groups to the DNA, mostly at CpG sites, to convert cytosine to 5-methylcytosine.

However it appears methylation can be in two types of Methylation; DNA Methylation or Protein (post-translational) Methylation [2][3], where histones are modified by adding methyl groups thus changing gene expression.

LSD1 (and JMJD2C[5]) actually works using the demethylation of histones. Which is this second Protein/post translational form of methylation. “LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9 (H3-K9), thereby leading to de-repression of androgen receptor target genes”[4]

Therefore both seem like valid ways to reexpressed silenced ARs. Prehaps these enzymes more so if histone methylation is in fact one of the normal/natural ways to AR expression is controlled? LSD1/JMJD2C also appear more directed to specifically demethylate ARs, which would appear to be safer.

But LSD1/JMJD2C should occur naturally in our bodies. Do we therefore need to purchase some from a lab and inject ourselves with it because higher serum levels will cause it to ‘work’ more? I guess theres only one way to find out.

[1] cancerres.aacrjournals.org/content/63/16/4984.full
[2] en.wikipedia.org/wiki/Methylation#Epigenetics
[3] en.wikipedia.org/wiki/Epigenetic_inheritance#DNA_methylation_and_chromatin_remodeling
[4] nature.com/nature/journal/v437/n7057/abs/nature04020.html
[5] ncbi.nlm.nih.gov/pubmed/17277772

youtube.com/watch?v=h4aJzcoIhfQ&feature=related