Influence of threonine metabolism on S-adenosylmethionine and histone methylation Academic Article uri icon


MeSH Major

  • Embryonic Stem Cells
  • Histones
  • Induced Pluripotent Stem Cells
  • Pluripotent Stem Cells
  • S-Adenosylmethionine
  • Threonine


  • 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.

publication date

  • January 11, 2013



  • Academic Article



  • eng

PubMed Central ID

  • PMC3652341

Digital Object Identifier (DOI)

  • 10.1126/science.1226603

PubMed ID

  • 23118012

Additional Document Info

start page

  • 222

end page

  • 6


  • 339


  • 6116