Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation
Ting Zhang1,2; Xiaowen Guan1,2; Un Lam Choi1,2; Qiang Dong3; Melody M. T. Lam1,2; Jianming Zeng1,2; Jun Xiong3; Xianju Wang1,2; Terence C. W. Poon1,2; Hongjie Zhang1,2; Xuanjun Zhang1,2; Hailin Wang5; Ruiyu Xie1,2; Bing Zhu3,4; Gang Li1,2

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.
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.
Together, our data demonstrated that AMPK is a critical regulator of myogenesis, partly through phosphorylating TET2.

KeywordAmpk Tet2 Phosphorylation Myogenesis Pax7
Indexed BySCIE
WOS Research AreaGenetics & Heredity
WOS SubjectGenetics & Heredity
WOS IDWOS:000470319200002
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Cited Times [WOS]:13   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
Faculty of Health Sciences
Affiliation1.Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau
2.Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau
3.National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
4.College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
5.The State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China
First Author AffilicationFaculty of Health Sciences;  Cancer Centre
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GB/T 7714
Ting Zhang,Xiaowen Guan,Un Lam Choi,et al. Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation[J]. EPIGENETICS & CHROMATIN,2019,12.
APA Ting Zhang,Xiaowen Guan,Un Lam Choi,Qiang Dong,Melody M. T. Lam,Jianming Zeng,Jun Xiong,Xianju Wang,Terence C. W. Poon,Hongjie Zhang,Xuanjun Zhang,Hailin Wang,Ruiyu Xie,Bing Zhu,&Gang Li.(2019).Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation.EPIGENETICS & CHROMATIN,12.
MLA Ting Zhang,et al."Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation".EPIGENETICS & CHROMATIN 12(2019).
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