Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation
	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
刊名	EPIGENETICS & CHROMATIN
	2019-06-04
卷号	12 页码:-
关键词	AMPK TET2 Phosphorylation Myogenesis PAX7
英文摘要	BackgroundTET-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.ResultsHere, we showed that AMP-activated protein kinase (AMPK) phosphorylates murine TET2 at the serine residue 97 (S97), andthe phosphorylation enhances TET2 stability through promoting its binding to 14-3-3. 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.ConclusionsTogether, our data demonstrated that AMPK is a critical regulator of myogenesis, partly through phosphorylating TET2.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/42988]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
作者单位	1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 2.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 3.Univ Macau, Fac Hlth Sci, Ave Univ, Taipa, Macau, Peoples R China 4.Univ Macau, Fac Hlth Sci, Canc Ctr, Taipa, Macau, Peoples R China 5.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Ting,Guan, Xiaowen,Choi, Un Lam,et al. Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation[J]. EPIGENETICS & CHROMATIN,2019,12:-.
APA	Zhang, Ting.,Guan, Xiaowen.,Choi, Un Lam.,Dong, Qiang.,Lam, Melody M. T..,...&Li, Gang.(2019).Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation.EPIGENETICS & CHROMATIN,12,-.
MLA	Zhang, Ting,et al."Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation".EPIGENETICS & CHROMATIN 12(2019):-.