Science (American Association for the Advancement of Science), 2013-01, Vol.339 (6116), p.222-226
2013
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Details
- Autor(en) / Beteiligte
- 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
- Quelle
- Science Online_科学在线
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1226603Titel-ID: cdi_proquest_miscellaneous_1808107446
- Format
- –
- Schlagworte
- Acetyl Coenzyme A - metabolism, Alcohol Oxidoreductases - metabolism, Amino acid metabolism, Amino acids, Animals, Cell Differentiation, Cells, Cultured, Cellular biology, Cellular metabolism, Cellular Reprogramming, Culture Media, Embryonic Stem Cells - cytology, Embryonic Stem Cells - metabolism, Enzymes, Epigenesis, Genetic, Fibroblasts - cytology, Fibroblasts - metabolism, Genetics, Glycine - metabolism, Histones, Histones - metabolism, Individualized Instruction, Induced Pluripotent Stem Cells - cytology, Induced Pluripotent Stem Cells - metabolism, Mass spectrometry, Metabolic Networks and Pathways, Metabolism, Metabolites, Methylation, Mice, Physiological regulation, Pluripotent Stem Cells - cytology, Pluripotent Stem Cells - metabolism, Protein metabolism, Proteins, S-Adenosylmethionine - metabolism, Stem cells, Threonine - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism