期刊
EPIGENETICS & CHROMATIN
卷 12, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13072-019-0281-x
关键词
AMPK; TET2; Phosphorylation; Myogenesis; PAX7
资金
- NSFC-FDCT Grant [033/2017/AFJ]
- Science and Technology Development Fund of Macau [137/2014/A3, 095/2015/A3]
- Research & Development Administration Office of the University of Macau [MYRG201700099, MYRG2018-00022]
- China Natural Science Foundation [31761163001]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据