Methionine Synthase Interacts With the Methionine Adenosyl‐Transferase MATα2 and the DNA Methyltransferase DNMT3b in the Nucleus
Abstract
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 14 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.
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BibTeX
@article{jeandel2026methionine,
title = {{Methionine Synthase Interacts With the Methionine Adenosyl‐Transferase MATα2 and the DNA Methyltransferase DNMT3b in the Nucleus}},
author = {Manon Jeandel and Jean‐marc Alberto and Okan Baspinar and Aurélie Robert and Natacha Dreumont and Zeinab Alsahly and David Meyre and Jean-Louis Guéant and David Coelho},
journal = {Journal of Inherited Metabolic Disease},
year = {2026},
month = jun,
doi = {10.1002/jimd.70211},
url = {https://hal.univ-lorraine.fr/hal-05752970v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Methionine Synthase Interacts With the Methionine Adenosyl‐Transferase MATα2 and the DNA Methyltransferase DNMT3b in the Nucleus
AU - Manon Jeandel
AU - Jean‐marc Alberto
AU - Okan Baspinar
AU - Aurélie Robert
AU - Natacha Dreumont
AU - Zeinab Alsahly
AU - David Meyre
AU - Jean-Louis Guéant
AU - David Coelho
PY - 2026
DA - 2026/06/17
JO - Journal of Inherited Metabolic Disease
DO - 10.1002/jimd.70211
UR - https://hal.univ-lorraine.fr/hal-05752970v1
AB - 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 14 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.
SN - 0141-8955
SN - 1573-2665
ER -