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Epigenetics and methylation is negatively affected by Poison/"Vitamin A"

Human genetics didn't all of a sudden "break" in the last 40 years.  Glyphosate/Roundup came along, which stops the breakdown of Poison/"Vitamin A", which then causes all sorts of problems...including the so-called undermethylation and overmethylation patterns.  They are both due to toxicity, and can be resolved by fixing the glyphosate and Poison/"Vitamin A" problems.  In short, your "methylation" problem is a glyphosate and Poison/"Vitamin A" toxicity problem, nothing more.

Retinoid compounds activate and induce hepatic glycine N-methyltransferase in rats.

Glycine N-methyltransferase (GNMT) functions to regulate S-adenosylmethionine (SAM) levels and the ratio of SAM/S-adenosylhomocysteine (SAH). SAM is a universal methyl group donor and the up-regulation of GNMT may lead to wastage of methyl groups required for transmethylation reactions. Previously, we demonstrated that dietary treatment of rats with 13-cis-retinoic acid (CRA) decreased the hepatic concentration of SAM and the SAH ratio. Here, we examined the ability of CRA, as well as all-trans-retinoic acid (ATRA), to regulate hepatic GNMT as a potential basis for our earlier observations. Rats were fed either a control (10% casein + 0.3% L-methionine) diet or a control diet supplemented with L-methionine (10 g/kg diet). Rats from each group were orally given ATRA, CRA (both at 30 micromol/kg body), or vehicle daily for 7 d. For control rats, administration of both CRA and ATRA elevated the hepatic GNMT activity 49% and 34%, respectively, compared with the control group. Similar results were exhibited by rats fed the methionine-supplemented diet. Moreover, the retinoid-induced elevations in enzyme activity were reflected in the abundance of GNMT protein. To our knowledge, this is the first report of a nutritional compound that induces GNMT activity at the transcriptional and/or translational level.

Retinoic acid and glucocorticoid treatment induce hepatic glycine N-methyltransferase and lower plasma homocysteine concentrations in rats and rat hepatoma cells.

Perturbation of folate and methyl group metabolism is associated with a number of pathological conditions, including cardiovascular disease and neoplastic development. Glycine N-methyltransferase (GNMT) is a key protein that functions to regulate the supply and utilization of methyl groups for S-adenosylmethionine (SAM)-dependent transmethylation reactions. Factors or conditions that have the ability to regulate GNMT and the generation of homocysteine, a product of transmethylation, have important implications in the potential perturbation of methyl group metabolism. We showed that retinoid compounds induce active hepatic GNMT, resulting in compromised transmethylation processes.

Retinoic acid targets DNA-methyltransferases and histone deacetylases during APL blast differentiation in vitro and in vivo

RA [Retinoic Acid] treatment induces epigenetic modifications at its target loci and restores myeloid differentiation of APL blasts. Using RA-sensitive and RA-resistant APL cell lines and primary blasts, we addressed the functional relevance of the aberrant methylation status at the RA-target promoter RARβ2 and the mechanism by which methylation is reversed by RA.

Hypermethylation-associated Inactivation of the Cellular Retinol-Binding-Protein 1 Gene in Human Cancer

Finally, we observed that a higher dietary retinol intake was associated with reduced frequencies of methylation of both genes.

Vitamin A induces inhibitory histone methylation modifications and down-regulates trained immunity in human monocytes.

Epidemiologic studies suggest that VAS has long-lasting immunomodulatory effects. We hypothesized that ATRA [All-Trans Retinoic Acid, a form of Poison/"Vitamin A"] inhibits inflammatory cytokines in a model of trained immunity in monocytes by inducing epigenetic reprogramming through histone modifications. We used an previously described in vitro model of trained immunity, in which adherent monocytes of healthy volunteers were incubated for 24 h with BCG in the presence or absence of ATRA. After washing the cells, they were incubated for an additional 6 d in culture medium and restimulated with microbial ligands, and cytokine production was assessed. ATRA inhibited cytokine responses upon restimulation of monocytes, and this effect was exerted through increased expression of SUV39H2, a histone methyltransferase that induces the inhibitory mark H3K9me3. H3K9me3 at promoter sites of several cytokines was up-regulated by ATRA, and inhibition of SUV39H2 restored cytokine production. In addition to H3K9me3, the stimulatory histone mark H3K4me3 was down-regulated by ATRA at several promoter locations of cytokine genes. Therefore, we can conclude that ATRA inhibits cytokine production in models of direct stimulation or BCG-induced trained immunity and that these effects are mediated by histone modifications.

Chromatin and DNA methylation dynamics during retinoic acid-induced RET gene transcriptional activation in neuroblastoma cells

Although it is well known that RET gene is strongly activated by retinoic acid (RA) in neuroblastoma cells, the mechanisms underlying such activation are still poorly understood. Here we show that a complex series of molecular events, that include modifications of both chromatin and DNA methylation state, accompany RA-mediated RET activation.

All-trans-Retinoic Acid Rapidly Induces Glycine N-methyltransferase in a Dose-Dependent Manner and Reduces Circulating Methionine and Homocysteine Levels in Rats

This work demonstrates that ATRA administration exerts a rapid effect on hepatic methyl group, folate and homocysteine metabolism at doses that are within the therapeutic range used by humans.

GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis.

Here we report that nuclear GlcNAcylation of a histone lysine methyltransferase (HKMT), MLL5, by O-GlcNAc transferase facilitates retinoic-acid-induced granulopoiesis in human HL60 promyelocytes through methylation of H3K4.

More will likely be added later. There's enough here for now to show a pattern.


Dr. Garrett Smith, the "Nutrition Detective"
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