Influence of Threonine Metabolism on S -Adenosylmethionine and Histone Methylation
Beth Israel Deaconess Medical Center · Howard Hughes Medical Institute · +5 more institutions
Abstract
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.…
Citation impact
- FWCI
- 16.79
- Percentile
- 100%
- References
- 25
Authors
13- NSNg Shyh‐Chang
Beth Israel Deaconess Medical Center, Howard Hughes Medical Institute, Harvard University, Dana-Farber Cancer Institute, Center for Systems Biology, Harvard Stem Cell Institute, Dana-Farber/Boston Children's Cancer and Blood Disorders Center
- JWJason W. Locasale
Beth Israel Deaconess Medical Center, Harvard University, Center for Systems Biology
- CACostas A. Lyssiotis
Beth Israel Deaconess Medical Center, Harvard University, Center for Systems Biology
- YZYu-Xiang Zheng
Beth Israel Deaconess Medical Center, Harvard University, Center for Systems Biology
- RYRen Yi Teo
Dana-Farber Cancer Institute, Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Topics & keywords
- Threonine
- Biology
- Reprogramming
- Epigenetics
- Histone
- Methylation
- Stem cell
- Biochemistry