TY - JOUR
T1 - Influence of threonine metabolism on S-adenosylmethionine and histone methylation
AU - Shyh-Chang, Ng
AU - Locasale, Jason W.
AU - Lyssiotis, Costas A.
AU - Zheng, Yuxiang
AU - Teo, Ren Yi
AU - Ratanasirintrawoot, Sutheera
AU - Zhang, Jin
AU - Onder, Tamer
AU - Unternaehrer, Juli J.
AU - Zhu, Hao
AU - Asara, John M.
AU - Daley, George Q.
AU - Cantley, Lewis C.
PY - 2013/1/11
Y1 - 2013/1/11
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1226603
DO - 10.1126/science.1226603
M3 - Article
C2 - 23118012
AN - SCOPUS:84872160110
SN - 0036-8075
VL - 339
SP - 222
EP - 226
JO - Science
JF - Science
IS - 6116
ER -