Phosphorylation of EZH2 by CDK1 and CDK2: A possible regulatory mechanism of transmission of the H3K27me3 epigenetic mark through cell divisions

Xianzhuo Zeng, Shuai Chen, Haojie Huang

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Histone H3 lysine 27 trimethylation (H3K27me3) catalyzed by the enzymatic subunit EZH2 in the Polycomb repressive complex 2 (PRC2) is essential for cells to 'memorize' gene expression patterns through cell divisions and plays an important role in establishing and maintaining cell identity during development. However, how the epigenetic mark is inherited through cell generations remains poorly understood. Recently, we and others demonstrate that CDK1 and CDK2 phosphorylate EZH2 at threonine 350 (T350) and that T350 phosphorylation is important for the binding of EZH2 to PRC2 recruiters, such as noncoding RNAs (ncRNAs) HOTAIR and XIST, and for the effective recruitment of PRC2 to EZH2 target loci in cells. These findings imply that phosphorylation of EZH2 by CDK1 and CDK2 may provide cells a mechanism that enhances EZH2 function during S and G2 phases of the cell cycle, thereby ensuring K27me3 on de novo synthesized H3 incorporated in nascent nucleosomes before sister chromosomes are divided into two daughter cells. Additionally, a potential role of T350 phosphorylation of EZH2 in differing EZH2 from its homolog EZH1 in catalyzing H3K27me3 as well as the interplay between phosphorylation at T350 and other residues [e.g., phosphorylation by p38 at threonine 372 (T372)] in governing EZH2 activity in proliferating versus non-dividing cells are also discussed. Together, CDK phosphorylation of EZH2 at T350 may represent a key regulatory mechanism of EZH2 function that is essential for the maintenance of H3K27me3 marks through cell divisions.

Original languageEnglish (US)
Pages (from-to)579-583
Number of pages5
JournalCell Cycle
Volume10
Issue number4
DOIs
StatePublished - Feb 15 2011
Externally publishedYes

Fingerprint

Epigenomics
Cell Division
Threonine
Phosphorylation
Polycomb Repressive Complex 2
Untranslated RNA
Nucleosomes
G2 Phase
S Phase
Histones
Lysine
Cell Cycle
Chromosomes
Maintenance
Gene Expression

Keywords

  • Cancer
  • CDK1
  • CDK2
  • Cell cycle
  • Epigenetics
  • EZH2
  • PRC2

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Phosphorylation of EZH2 by CDK1 and CDK2 : A possible regulatory mechanism of transmission of the H3K27me3 epigenetic mark through cell divisions. / Zeng, Xianzhuo; Chen, Shuai; Huang, Haojie.

In: Cell Cycle, Vol. 10, No. 4, 15.02.2011, p. 579-583.

Research output: Contribution to journalArticle

@article{8983fa808a0a4fb1ae8a55dd4a8caedc,
title = "Phosphorylation of EZH2 by CDK1 and CDK2: A possible regulatory mechanism of transmission of the H3K27me3 epigenetic mark through cell divisions",
abstract = "Histone H3 lysine 27 trimethylation (H3K27me3) catalyzed by the enzymatic subunit EZH2 in the Polycomb repressive complex 2 (PRC2) is essential for cells to 'memorize' gene expression patterns through cell divisions and plays an important role in establishing and maintaining cell identity during development. However, how the epigenetic mark is inherited through cell generations remains poorly understood. Recently, we and others demonstrate that CDK1 and CDK2 phosphorylate EZH2 at threonine 350 (T350) and that T350 phosphorylation is important for the binding of EZH2 to PRC2 recruiters, such as noncoding RNAs (ncRNAs) HOTAIR and XIST, and for the effective recruitment of PRC2 to EZH2 target loci in cells. These findings imply that phosphorylation of EZH2 by CDK1 and CDK2 may provide cells a mechanism that enhances EZH2 function during S and G2 phases of the cell cycle, thereby ensuring K27me3 on de novo synthesized H3 incorporated in nascent nucleosomes before sister chromosomes are divided into two daughter cells. Additionally, a potential role of T350 phosphorylation of EZH2 in differing EZH2 from its homolog EZH1 in catalyzing H3K27me3 as well as the interplay between phosphorylation at T350 and other residues [e.g., phosphorylation by p38 at threonine 372 (T372)] in governing EZH2 activity in proliferating versus non-dividing cells are also discussed. Together, CDK phosphorylation of EZH2 at T350 may represent a key regulatory mechanism of EZH2 function that is essential for the maintenance of H3K27me3 marks through cell divisions.",
keywords = "Cancer, CDK1, CDK2, Cell cycle, Epigenetics, EZH2, PRC2",
author = "Xianzhuo Zeng and Shuai Chen and Haojie Huang",
year = "2011",
month = "2",
day = "15",
doi = "10.4161/cc.10.4.14722",
language = "English (US)",
volume = "10",
pages = "579--583",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "4",

}

TY - JOUR

T1 - Phosphorylation of EZH2 by CDK1 and CDK2

T2 - A possible regulatory mechanism of transmission of the H3K27me3 epigenetic mark through cell divisions

AU - Zeng, Xianzhuo

AU - Chen, Shuai

AU - Huang, Haojie

PY - 2011/2/15

Y1 - 2011/2/15

N2 - Histone H3 lysine 27 trimethylation (H3K27me3) catalyzed by the enzymatic subunit EZH2 in the Polycomb repressive complex 2 (PRC2) is essential for cells to 'memorize' gene expression patterns through cell divisions and plays an important role in establishing and maintaining cell identity during development. However, how the epigenetic mark is inherited through cell generations remains poorly understood. Recently, we and others demonstrate that CDK1 and CDK2 phosphorylate EZH2 at threonine 350 (T350) and that T350 phosphorylation is important for the binding of EZH2 to PRC2 recruiters, such as noncoding RNAs (ncRNAs) HOTAIR and XIST, and for the effective recruitment of PRC2 to EZH2 target loci in cells. These findings imply that phosphorylation of EZH2 by CDK1 and CDK2 may provide cells a mechanism that enhances EZH2 function during S and G2 phases of the cell cycle, thereby ensuring K27me3 on de novo synthesized H3 incorporated in nascent nucleosomes before sister chromosomes are divided into two daughter cells. Additionally, a potential role of T350 phosphorylation of EZH2 in differing EZH2 from its homolog EZH1 in catalyzing H3K27me3 as well as the interplay between phosphorylation at T350 and other residues [e.g., phosphorylation by p38 at threonine 372 (T372)] in governing EZH2 activity in proliferating versus non-dividing cells are also discussed. Together, CDK phosphorylation of EZH2 at T350 may represent a key regulatory mechanism of EZH2 function that is essential for the maintenance of H3K27me3 marks through cell divisions.

AB - Histone H3 lysine 27 trimethylation (H3K27me3) catalyzed by the enzymatic subunit EZH2 in the Polycomb repressive complex 2 (PRC2) is essential for cells to 'memorize' gene expression patterns through cell divisions and plays an important role in establishing and maintaining cell identity during development. However, how the epigenetic mark is inherited through cell generations remains poorly understood. Recently, we and others demonstrate that CDK1 and CDK2 phosphorylate EZH2 at threonine 350 (T350) and that T350 phosphorylation is important for the binding of EZH2 to PRC2 recruiters, such as noncoding RNAs (ncRNAs) HOTAIR and XIST, and for the effective recruitment of PRC2 to EZH2 target loci in cells. These findings imply that phosphorylation of EZH2 by CDK1 and CDK2 may provide cells a mechanism that enhances EZH2 function during S and G2 phases of the cell cycle, thereby ensuring K27me3 on de novo synthesized H3 incorporated in nascent nucleosomes before sister chromosomes are divided into two daughter cells. Additionally, a potential role of T350 phosphorylation of EZH2 in differing EZH2 from its homolog EZH1 in catalyzing H3K27me3 as well as the interplay between phosphorylation at T350 and other residues [e.g., phosphorylation by p38 at threonine 372 (T372)] in governing EZH2 activity in proliferating versus non-dividing cells are also discussed. Together, CDK phosphorylation of EZH2 at T350 may represent a key regulatory mechanism of EZH2 function that is essential for the maintenance of H3K27me3 marks through cell divisions.

KW - Cancer

KW - CDK1

KW - CDK2

KW - Cell cycle

KW - Epigenetics

KW - EZH2

KW - PRC2

UR - http://www.scopus.com/inward/record.url?scp=79951909917&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951909917&partnerID=8YFLogxK

U2 - 10.4161/cc.10.4.14722

DO - 10.4161/cc.10.4.14722

M3 - Article

C2 - 21278485

AN - SCOPUS:79951909917

VL - 10

SP - 579

EP - 583

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 4

ER -