Influence of threonine metabolism on S-adenosylmethionine and histone methylation.
basic_science · Level V
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- Record sourced from PubMed, PMID 23118012.
- Also identified by DOI 10.1126/science.1226603 and PMC identifier 3652341.
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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.
Medical subject headings
- Embryonic Stem Cells
- Histones
- Induced Pluripotent Stem Cells
- Pluripotent Stem Cells
- S-Adenosylmethionine
- Threonine