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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; et al.

(Profiled Author: Hao Zhu)

Science. 2013;339(6116):222-226.

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.


PMID: 23118012     PMCID: PMC3652341    

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