Influence of threonine metabolism on S-adenosylmethionine and histone methylation.
Influence of threonine metabolism on S-adenosylmethionine and histone methylation.
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DOI：
10.1126/science.1226603
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发表时间：
2013-01-11
期刊：
影响因子：
--
通讯作者：
Cantley LC
中科院分区：
文献类型：
--
作者：
Shyh-Chang N;Locasale JW;Lyssiotis CA;Zheng Y;Teo RY;Ratanasirintrawoot S;Zhang J;Onder T;Unternaehrer JJ;Zhu H;Asara JM;Daley GQ;Cantley LC
苏氨酸是小鼠胚胎干细胞（mESCs）多能性所关键必需的唯一一种氨基酸，但其详细机制仍不清楚。我们发现，在多能干细胞中苏氨酸（Thr）和S - 腺苷甲硫氨酸（SAM）的代谢是相互关联的，从而导致组蛋白甲基化的调控。对mESCs的同位素标记显示，苏氨酸为细胞甘氨酸（Gly）以及SAM合成所需的乙酰辅酶A（CoA）提供了相当大的一部分。从培养基中去除苏氨酸或者从mESCs中去除苏氨酸脱氢酶（Tdh）会减少SAM的积累，并降低组蛋白H3赖氨酸 - 4（H3K4me3）的三甲基化，导致生长减缓以及分化增加。因此，SAM的含量似乎影响H3K4me3，这为代谢途径的调节可能影响干细胞命运提供了一种可能的机制。
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 (Thr) and S-adenosyl-methionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that Thr provides a substantial fraction of both the cellular glycine (Gly) and the acetyl-coenzyme A (CoA) needed for SAM synthesis. Depletion of Thr from the culture medium or threonine dehydrogenase (Tdh) from mESCs decreased accumulation of SAM and decreased tri-methylation 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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DOI：
10.1073/pnas.1111312108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Alexander, Peter B.;Wang, Jian;McKnight, Steven L.
通讯作者：
McKnight, Steven L.
影响因子：
4.8
作者：
Zee, Barry M.;Levin, Rebecca S.;Garcia, Benjamin A.
通讯作者：
Garcia, Benjamin A.
影响因子：
64.8
作者：
Possemato, Richard;Marks, Kevin M.;Shaul, Yoav D.;Pacold, Michael E.;Kim, Dohoon;Birsoy, Kivanc;Sethumadhavan, Shalini;Woo, Hin-Koon;Jang, Hyun G.;Jha, Abhishek K.;Chen, Walter W.;Barrett, Francesca G.;Stransky, Nicolas;Tsun, Zhi-Yang;Cowley, Glenn S.;Barretina, Jordi;Kalaany, Nada Y.;Hsu, Peggy P.;Ottina, Kathleen;Chan, Albert M.;Yuan, Bingbing;Garraway, Levi A.;Root, David E.;Mino-Kenudson, Mari;Brachtel, Elena F.;Driggers, Edward M.;Sabatini, David M.
通讯作者：
Sabatini, David M.
影响因子：
64.5
作者：
Ang YS;Tsai SY;Lee DF;Monk J;Su J;Ratnakumar K;Ding J;Ge Y;Darr H;Chang B;Wang J;Rendl M;Bernstein E;Schaniel C;Lemischka IR
通讯作者：
Lemischka IR
影响因子：
23.9
作者：
Stadtfeld, Matthias;Maherali, Nimet;Hochedlinger, Konrad
通讯作者：
Hochedlinger, Konrad