Nrf2's ability to activate is dependent on methylation

Protein methylation and Nrf2.

Highlights

• Ability of Nrf2 to activate target genes depends on methylation of the Nrf2 protein and is reduced by increased level of SAH.

• Stretched conclusion: B12/folate deficiency lowers Nrf2 influence due to increased level of SAH.

Findings

(I) I recently shared a study which shows that methylation of the arginine residue of the Nrf2 protein increases its DNA binding (which is good):

“we found that methylation of Nrf2 by PRMT1 led to a moderate increase of its DNA-binding activity and transactivation, which subsequently protected cells against the tBHP-induced glutathione depletion and cell death. (R1)

Collectively, our results define a novel modification of Nrf2, which operates as a fine-tuning mechanism for the transcriptional activity of Nrf2 under the oxidative stress.”

(II) Another paper demonstrates that methylation of arginine residues of the proteins is affected negatively by the level of SAH (AdoHcy) more than DNA methylation:

“our results indicate that protein arginine methylation is more sensitive to AdoHcy accumulation than DNA methylation, pinpointing a possible new player in methylation-related pathology.” (R2)