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Updated: May 17, 2026

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
Influence of threonine metabolism on S-adenosylmethionine and histone methylation
Ng Shyh-Chang1, Jason W Locasale, Costas A Lyssiotis
1Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Abstract:
Threonine is the only amino acid critically required for the pluripotency of mouse embryonic stem cells (mESCs), but the detailed mechanism remains unclear. We found that threonine and S-adenosylmethionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that threonine provides a substantial fraction of both the cellular glycine and the acetyl-coenzyme A (CoA) needed for SAM synthesis. Depletion of threonine from the culture medium or threonine dehydrogenase (Tdh) from mESCs decreased accumulation of SAM and decreased trimethylation of histone H3 lysine 4 (H3K4me3), leading to slowed growth and increased differentiation. Thus, abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate.
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