Influence of threonine metabolism on S-adenosylmethionine and histone methylation

Ng Shyh-Chang, Jason W. Locasale, Costas A. Lyssiotis, Yuxiang Zheng, Ren Yi Teo, Sutheera Ratanasirintrawoot, Jin Zhang, Tamer Onder, Juli J. Unternaehrer, Hao Zhu, John M. Asara, George Q. Daley, Lewis C. Cantley

Research output: Contribution to journalArticlepeer-review

462 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)222-226
Number of pages5
Issue number6116
StatePublished - Jan 11 2013

ASJC Scopus subject areas

  • General


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