Influence of Threonine Metabolism on S-Adenosylmethionine and Histone Methylation

被引：508

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

共 24 条

[1] Targeted killing of a mammalian cell based upon its specialized metabolic state [J].

Alexander, Peter B. ;

Wang, Jian ;

McKnight, Steven L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (38) :15828-15833

[2] Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network [J].

Ang, Yen-Sin ;

Tsai, Su-Yi ;

Lee, Dung-Fang ;

Monk, Jonathan ;

Su, Jie ;

Ratnakumar, Kajan ;

Ding, Junjun ;

Ge, Yongchao ;

Darr, Henia ;

Chang, Betty ;

Wang, Jianlong ;

Rendl, Michael ;

Bernstein, Emily ;

Schaniel, Christoph ;

Lemischka, Ihor R. .

CELL, 2011, 145 (02) :183-197

[3] Chromatin signatures of pluripotent cell lines [J].

Azuara, V ;

Perry, P ;

Sauer, S ;

Spivakov, M ;

Jorgensen, HF ;

John, RM ;

Gouti, M ;

Casanova, M ;

Warnes, G ;

Merkenschlager, M ;

Fisher, AG .

NATURE CELL BIOLOGY, 2006, 8 (05) :532-U189

[4] EFFECTS OF THE S-ADENOSYLHOMOCYSTEINE HYDROLASE INHIBITORS 3-DEAZAADENOSINE AND 3-DEAZAARISTEROMYCIN ON RNA METHYLATION AND SYNTHESIS [J].

BACKLUND, PS ;

CAROTTI, D ;

CANTONI, GL .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1986, 160 (02) :245-251

[5] Genome-Wide Kinetics of Nucleosome Turnover Determined by Metabolic Labeling of Histones [J].

Deal, Roger B. ;

Henikoff, Jorja G. ;

Henikoff, Steven .

SCIENCE, 2010, 328 (5982) :1161-1164

[6]

EAGLE H, 1961, J BIOL CHEM, V236, P2039

[7] Open chromatin in pluripotency and reprogramming [J].

Gaspar-Maia, Alexandre ;

Alajem, Adi ;

Meshorer, Eran ;

Ramalho-Santos, Miguel .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2011, 12 (01) :36-47

[8] Proteomic analysis of organ-specific post-translational lysine acetylation and -methylation in mice by use of anti-acetyllysine and -methyllysine mouse monoclonal antibodies [J].

Iwabata, H ;

Yoshida, M ;

Komatsu, Y .

PROTEOMICS, 2005, 5 (18) :4653-4664

[9] Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation [J].

Jain, Mohit ;

Nilsson, Roland ;

Sharma, Sonia ;

Madhusudhan, Nikhil ;

Kitami, Toshimori ;

Souza, Amanda L. ;

Kafri, Ran ;

Kirschner, Marc W. ;

Clish, Clary B. ;

Mootha, Vamsi K. .

SCIENCE, 2012, 336 (6084) :1040-1044

[10] Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis [J].

Locasale, Jason W. ;

Grassian, Alexandra R. ;

Melman, Tamar ;

Lyssiotis, Costas A. ;

Mattaini, Katherine R. ;

Bass, Adam J. ;

Heffron, Gregory ;

Metallo, Christian M. ;

Muranen, Taru ;

Sharfi, Hadar ;

Sasaki, Atsuo T. ;

Anastasiou, Dimitrios ;

Mullarky, Edouard ;

Vokes, Natalie I. ;

Sasaki, Mika ;

Beroukhim, Rameen ;

Stephanopoulos, Gregory ;

Ligon, Azra H. ;

Meyerson, Matthew ;

Richardson, Andrea L. ;

Chin, Lynda ;

Wagner, Gerhard ;

Asara, John M. ;

Brugge, Joan S. ;

Cantley, Lewis C. ;

Vander Heiden, Matthew G. .

NATURE GENETICS, 2011, 43 (09) :869-U79

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