Methionine Synthase Interacts With the Methionine Adenosyl-Transferase MATα2 and the DNA Methyltransferase DNMT3b in the Nucleus.

Fiche publication

Date publication

juillet 2026

Journal

Journal of inherited metabolic disease

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GUEANT Jean-Louis , Dr DREUMONT Natacha , Pr MEYRE David , Dr COELHO David

Tous les auteurs :
Jeandel M, Alberto JM, Baspinar O, Robert A, Dreumont N, Alsahly Z, Meyre D, Guéant JL, Coelho D

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42309558

Résumé

Transmethylation reactions, which are crucial for regulating gene expression, require S-adenosyl-L-methionine (SAM) as methyl donor. The substrate for SAM synthesis is methionine, which can be produced by methionine synthase (MS) whose dysfunctions are associated with SAM synthesis alterations despite the presence of methionine in the milieu, suggesting a preferential use of the methionine produced de novo. This highlights the crucial role of MS activity and would imply nuclear import of SAM or MS nuclear localization, allowing protein-protein interactions with the methionine adenosyl-transferases (MAT) responsible for SAM production. Using subcellular fractions of human cells, biochemical and cellular approaches, including incorporation of C-methyltetrahydrofolate, here we provide the experimental evidence of MS localization and activity in the nucleus where it interacts with MATα2, the catalytic subunit of MATII, and the methyltransferase DNMT3b. These results support the idea that spatial compartmentalization of one-carbon metabolism could play a major role in regulating the epigenome.