Influence of Threonine Metabolism on S -Adenosylmethionine and Histone Methylation

Author:

Shyh-Chang Ng12345,Locasale Jason W.56,Lyssiotis Costas A.56,Zheng Yuxiang56,Teo Ren Yi1,Ratanasirintrawoot Sutheera123,Zhang Jin123,Onder Tamer123,Unternaehrer Juli J.123,Zhu Hao123,Asara John M.5,Daley George Q.1234,Cantley Lewis C.56

Affiliation:

1. Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Boston Children’s Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA.

2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

3. Harvard Stem Cell Institute, Cambridge, MA 02138, USA.

4. Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.

5. Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

6. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

SAM, Histones, and Stem Cells Mouse embryonic stem cells require threonine for growth and express large amounts of the enzyme that catalyzes the first step in threonine metabolism. To find out what is so important about threonine in these cells, Shyh-Change et al. (p. 222 , published online 1 November; see the Perspective by Sassone-Corsi ) monitored changes in metabolism by mass spectrometry in induced pluripotent stem cells. Threonine was required to maintain cellular concentrations of S-adenosylmethionine (SAM), a substrate used for protein methylation. Restriction of threonine inhibited methylation of histones, which is characteristic of chromatin in embryonic stem cells. Thus, altered metabolism of threonine and methionine in stem cells may be linked to epigenetic changes that influence genetic reprogramming and decisions of stem cells to proliferate or differentiate.

Funder

National Institutes of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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