Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism
By S. Mentch, Mahya Merhmohamadi, Lei Huang, Xiaojing Liu, D. Gupta, Dwight A. L. Mattocks, Paola Gomez, G. Ables, M. Bamman, A. Thalacker-Mercer and 2 more. Cell Metabolism, 2015
607 citations recorded by the source corpus.
Summary S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) link one-carbon metabolism to methylation status. However it is unknown whether regulation of SAM and SAH by nutrient availability can be directly sensed to alter the kinetics of key histone methylation marks. We provide evidence that the status of methionine metabolism is sufficient to determine levels of histone methylation by modulating SAM and SAH. This dynamic interaction led to rapid changes in H3K4me3, altered gene transcription, provided feedback regulation to one-carbon metabolism and could be fully recovered upon restoration of methionine. Modulation of methionine in diet led to changes in metabolism and histone methylation in liver. In humans, methionine variability in fasting serum was commensurate with concentrations needed for these dynamics and could be partly explained by diet. Together these findings demonstrate that flux through methionine metabolism and the sensing of methionine availability may allow for direct communication to the chromatin state in cells.
Subfields: Biochemistry, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7e6496e676374a981314cf1deb9cd281c626fa91
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In Molecular Biology
Citations in the corpus
- Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “Under methionine-limiting conditions, SAM, SAH and the SAM/SAH ratio are dynamically regulated, which reduces the H3K4me3 level and affects the expression of methylationrelated enzymes (Mentch et al., 2015).”