Hypermethylation of D2 receptor in TS
Does anybody have a good understanding about what affects DNA methylation / demethylation dynamics? E.g. are there any specific substrates (besides SAMe of course) that have strong influence of the process?
I’m interested in this because it seems that a cell can get stuck in a state of silenced genes because of something.
Relevant example is hypermethylation of Dopamine R2 and hypomethylation of DAT (dopamine transporter) in the Tourette syndrome.
There has to be a reason for this phenomena and since tics can be acquired via brain trauma or psychologic stress it means that something changes in the neuronal metabolism that leads to the malfunction.
From comments
Just found a possible clue:
The TET enzymes that are involved in demethylation of DNA, require AKG and oxygen as substrates, Zinc and Iron (Fe2+) as cofactors. (R2).
Perhaps it’s the low availability of the substrates and cofactors that impact demethylation capacity inside the cell.
I can see how high oxidative stress or B1 deficiency can lower AKG synthesis, and how iron availability is reduced due to dietary restrictions or again high oxidative stress.