Influence of Threonine Metabolism on S-Adenosylmethionine and Histone Methylation

• Autores: Ng Shyh Chang, Yuxiang Zheng, Sutheera Ratanasirintrawoot
• Localización: Science, ISSN 0036-8075, Vol. 339, Nº 6116, 2013, págs. 223-226
• Idioma: inglés
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• Resumen

  • 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.