Details

Autor(en) / Beteiligte

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

Titel

Influence of Threonine Metabolism on S-Adenosylmethionine and Histone Methylation

Ist Teil von

• Science (American Association for the Advancement of Science), 2013-01, Vol.339 (6116), p.222-226

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2013

Link zum Volltext

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.