S-adenosylmethionine supply controls DNA methylation turnover in synovial sarcoma

In synovial sarcoma cell line models, MAT2A inhibition drops intracellular SAM from 94 uM to 5.6 uM within 24 hours and slows global 5-methyldeoxycytosine turnover by 19%.

• Why it matters: SAM availability links nutrient and metabolic disruptions to chromatin methylation dynamics, but how this specifically reshapes DNA methylation and gene expression in synovial sarcoma was unclear.
• What they did: Cells were treated with azacitidine or the MAT2A inhibitor AG-270; SAM was quantified by liquid chromatography-mass spectrometry, methylation turnover by [2H3-methyl]-methionine stable isotope tracing, and methylation sites by EM-seq with transcriptional changes by RNA-seq.
• The result: SAM depletion redistributed DNA methylation (loss at 252 sites, gain at 206) without promoter methylation changes at altered genes, while both treatments activated mesenchymal genes and suppressed cell cycle progression.

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