Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2

Shuai Chen, Laura R. Bohrer, Aswathy N. Rai, Yunqian Pan, Lu Gan, Xianzheng Zhou, Anindya Bagchi, Jeffrey A. Simon, Haojie Huang

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

The Polycomb group (PcG) protein, enhancer of zeste homologue 2 (EZH2), has an essential role in promoting histone H3 lysine 27 trimethylation (H3K27me3) and epigenetic gene silencing. This function of EZH2 is important for cell proliferation and inhibition of cell differentiation, and is implicated in cancer progression. Here, we demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) phosphorylate EZH2 at Thr 350 in an evolutionarily conserved motif. Phosphorylation of Thr 350 is important for recruitment of EZH2 and maintenance of H3K27me3 levels at EZH2-target loci. Blockage of Thr 350 phosphorylation not only diminishes the global effect of EZH2 on gene silencing, it also mitigates EZH2-mediated cell proliferation and migration. These results demonstrate that CDK-mediated phosphorylation is a key mechanism governing EZH2 function and that there is a link between the cell-cycle machinery and epigenetic gene silencing.

Original languageEnglish (US)
Pages (from-to)1108-1114
Number of pages7
JournalNature Cell Biology
Volume12
Issue number11
DOIs
StatePublished - Nov 2010
Externally publishedYes

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Cyclin-Dependent Kinases
Gene Silencing
Epigenomics
Phosphorylation
Polycomb-Group Proteins
Cell Proliferation
CDC2 Protein Kinase
Cyclin-Dependent Kinase 2
Enhancer of Zeste Homolog 2 Protein
Histones
Lysine
Cell Movement
Cell Differentiation
Cell Cycle
Maintenance

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. / Chen, Shuai; Bohrer, Laura R.; Rai, Aswathy N.; Pan, Yunqian; Gan, Lu; Zhou, Xianzheng; Bagchi, Anindya; Simon, Jeffrey A.; Huang, Haojie.

In: Nature Cell Biology, Vol. 12, No. 11, 11.2010, p. 1108-1114.

Research output: Contribution to journalArticle

Chen, S, Bohrer, LR, Rai, AN, Pan, Y, Gan, L, Zhou, X, Bagchi, A, Simon, JA & Huang, H 2010, 'Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2', Nature Cell Biology, vol. 12, no. 11, pp. 1108-1114. https://doi.org/10.1038/ncb2116
Chen, Shuai ; Bohrer, Laura R. ; Rai, Aswathy N. ; Pan, Yunqian ; Gan, Lu ; Zhou, Xianzheng ; Bagchi, Anindya ; Simon, Jeffrey A. ; Huang, Haojie. / Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. In: Nature Cell Biology. 2010 ; Vol. 12, No. 11. pp. 1108-1114.
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abstract = "The Polycomb group (PcG) protein, enhancer of zeste homologue 2 (EZH2), has an essential role in promoting histone H3 lysine 27 trimethylation (H3K27me3) and epigenetic gene silencing. This function of EZH2 is important for cell proliferation and inhibition of cell differentiation, and is implicated in cancer progression. Here, we demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) phosphorylate EZH2 at Thr 350 in an evolutionarily conserved motif. Phosphorylation of Thr 350 is important for recruitment of EZH2 and maintenance of H3K27me3 levels at EZH2-target loci. Blockage of Thr 350 phosphorylation not only diminishes the global effect of EZH2 on gene silencing, it also mitigates EZH2-mediated cell proliferation and migration. These results demonstrate that CDK-mediated phosphorylation is a key mechanism governing EZH2 function and that there is a link between the cell-cycle machinery and epigenetic gene silencing.",
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AU - Zhou, Xianzheng

AU - Bagchi, Anindya

AU - Simon, Jeffrey A.

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