Influence of Threonine Metabolism on S-Adenosylmethionine and Histone Methylation

被引：501

作者：

Ng Shyh-Chang ^{[1
,2
,3
,4
,5
,6
,7
]}

Locasale, Jason W. ^{[6
,7
]}

Lyssiotis, Costas A. ^{[6
,7
]}

Zheng, Yuxiang ^{[6
,7
]}

Teo, Ren Yi ^{[1
,2
]}

Ratanasirintrawoot, Sutheera ^{[1
,2
,3
,4
]}

Zhang, Jin ^{[1
,2
,3
,4
]}

Onder, Tamer ^{[1
,2
,3
,4
]}

Unternaehrer, Juli J. ^{[1
,2
,3
,4
]}

Zhu, Hao ^{[1
,2
,3
,4
]}

Asara, John M. ^{[6
]}

Daley, George Q. ^{[1
,2
,3
,4
,5
]}

Cantley, Lewis C. ^{[6
,7
]}

机构：

[1] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[4] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[5] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[6] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Dept Med, Boston, MA 02215 USA

[7] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

SCIENCE | 2013年 / 339卷 / 6116期

关键词：

EMBRYONIC STEM-CELLS; SELF-RENEWAL; MOUSE; GLYCINE; CANCER; CHROMATIN;

D O I：

10.1126/science.1226603

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：222 / 226

页数：5

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