CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic diffe
Author: ["Yongkun Wei","Ya-Huey Chen","Long-Yuan Li","Jingyu Lang","Su-Peng Yeh","Bin Shi","Cheng-Chieh Yang","Jer-Yen Yang","Chun-Yi Lin","Chien-Chen Lai","Mien-Chie Hung"]
Publication: Nature Cell Biology
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Abstract
The Polycomb group protein EZH2 promotes trimethylation of histone H3K27 and gene silencing. Cdk1 is found to phosphorylate EZH2 to inhibit its methyltransferase activity, affecting EZH2-target genes involved in osteogenic differentiation. Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyses the trimethylation of histone H3 on Lys 27 (H3K27), which represses gene transcription. EZH2 enhances cancer-cell invasiveness and regulates stem cell differentiation. Here, we demonstrate that EZH2 can be phosphorylated at Thr 487 through activation of cyclin-dependent kinase 1 (CDK1). The phosphorylation of EZH2 at Thr 487 disrupted EZH2 binding with the other PRC2 components SUZ12 and EED, and thereby inhibited EZH2 methyltransferase activity, resulting in inhibition of cancer-cell invasion. In human mesenchymal stem cells, activation of CDK1 promoted mesenchymal stem cell differentiation into osteoblasts through phosphorylation of EZH2 at Thr 487. These findings define a signalling link between CDK1 and EZH2 that may have an important role in diverse biological processes, including cancer-cell invasion and osteogenic differentiation of mesenchymal stem cells.
Cite this article
Wei, Y., Chen, YH., Li, LY. et al. CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nat Cell Biol 13, 87–94 (2011). https://doi.org/10.1038/ncb2139
