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- Title
Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation.
- Authors
Zhang, Ting; Guan, Xiaowen; Choi, Un Lam; Dong, Qiang; Lam, Melody M. T.; Zeng, Jianming; Xiong, Jun; Wang, Xianju; Poon, Terence C. W.; Zhang, Hongjie; Zhang, Xuanjun; Wang, Hailin; Xie, Ruiyu; Zhu, Bing; Li, Gang
- Abstract
Background: TET-mediated oxidation of 5-mC participates in both passive and active DNA demethylation, which exerts a significant influence on diverse biological processes. Mass spectrometry has identified multiple phosphorylation sites of TET2. However, the functions of these phosphosites and their corresponding kinases are mostly unknown. Results: Here, we showed that AMP-activated protein kinase (AMPK) phosphorylates murine TET2 at the serine residue 97 (S97), and the phosphorylation enhances TET2 stability through promoting its binding to 14-3-3β. AMPK ablation resulted in decreased global 5-hmC levels at the myotube stages, severe differentiation defects of C2C12 cells and significantly, total loss of expression of Pax7. Genome-wide analyses revealed increased DNA methylation at genic and enhancer regions of AMPK-null myoblasts and myotubes. Using CRISPR/Cas9 technology, we showed that a novel enhancer, which is hypermethylated in AMPK-null cells, regulates Pax7 expression. The phospho-mimicking mutant, TET2-S97E, could partly rescue the differentiation defect in AMPK-ablated C2C12 cells. Conclusions: Together, our data demonstrated that AMPK is a critical regulator of myogenesis, partly through phosphorylating TET2.
- Subjects
MYOBLASTS; PHOSPHORYLATION; PROTEIN kinases; DNA demethylation; MASS spectrometry; DNA methylation; KINASES
- Publication
Epigenetics & Chromatin, 2019, Vol 12, Issue 1, pN.PAG
- ISSN
1756-8935
- Publication type
Article
- DOI
10.1186/s13072-019-0281-x