Molecular Cell

, volume 70 , issue 3 , pages 435-44800000

Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2

Chul Hwan Lee ^{1, 2}

Marlene Holder ³

Daniel Grau ³

Ricardo Saldaña Meyer ^{1, 2}

Jia Ray Yu ^{1, 2}

Rais Ahmad Ganai ^{1, 2}

Jenny Zhang ³

Miao Wang ³

Gary Leroy ^{1, 2}

Marc Werner Dobenecker ⁴

Danny Reinberg ^{1, 2}

Karim-Jean Armache ³

Hide authors affiliations Show authors affiliations: 4 affiliations

Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA |

Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA |

Skirball Institute of Biomolecular Medicine, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA |

⁴

Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, NY 10065, USA |

Publication type: Journal Article

Publication date: 2018-05-01

Elsevier

Molecular Cell

scimago Q1

wos Q1

SJR: 9.051

CiteScore: 24.4

Impact factor: 16.6

ISSN: 10972765, 10974164

DOI: 10.1016/j.molcel.2018.03.019

Copy DOI

PubMed ID: 29681498

Molecular Biology

Cell Biology

Abstract

The maintenance of gene expression patterns during metazoan development is achieved, in part, by the actions of polycomb repressive complex 2 (PRC2). PRC2 catalyzes mono-, di-, and trimethylation of histone H3 at lysine 27 (H3K27), with H3K27me2/3 being strongly associated with silenced genes. We demonstrate that EZH1 and EZH2, the two mutually exclusive catalytic subunits of PRC2, are differentially activated by various mechanisms. Whereas both PRC2-EZH1 and PRC2-EZH2 are able to catalyze mono- and dimethylation, only PRC2-EZH2 is strongly activated by allosteric modulators and specific chromatin substrates to catalyze trimethylation of H3K27 in mouse embryonic stem cells (mESCs). However, we also show that a PRC2-associated protein, AEBP2, can stimulate the activity of both complexes through a mechanism independent of and additive to allosteric activation. These results have strong implications regarding the cellular requirements for and the accompanying adjustments in PRC2 activity, given the differential expression of EZH1 and EZH2 upon cellular differentiation.

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GOST |

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GOST Copy

Lee C. H. et al. Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2 // Molecular Cell. 2018. Vol. 70. No. 3. pp. 435-44800000.

GOST all authors (up to 50) Copy

Lee C. H., Holder M., Grau D., Saldaña Meyer R., Yu J. R., Ganai R. A., Zhang J., Wang M., Leroy G., Dobenecker M. W., Reinberg D., Armache K. Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2 // Molecular Cell. 2018. Vol. 70. No. 3. pp. 435-44800000.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1016/j.molcel.2018.03.019

UR - https://doi.org/10.1016/j.molcel.2018.03.019

TI - Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2

T2 - Molecular Cell

AU - Lee, Chul Hwan

AU - Holder, Marlene

AU - Grau, Daniel

AU - Saldaña Meyer, Ricardo

AU - Yu, Jia Ray

AU - Ganai, Rais Ahmad

AU - Zhang, Jenny

AU - Wang, Miao

AU - Leroy, Gary

AU - Dobenecker, Marc Werner

AU - Reinberg, Danny

AU - Armache, Karim-Jean

PY - 2018

DA - 2018/05/01

PB - Elsevier

SP - 435-44800000

IS - 3

VL - 70

PMID - 29681498

SN - 1097-2765

SN - 1097-4164

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2018_Lee,

author = {Chul Hwan Lee and Marlene Holder and Daniel Grau and Ricardo Saldaña Meyer and Jia Ray Yu and Rais Ahmad Ganai and Jenny Zhang and Miao Wang and Gary Leroy and Marc Werner Dobenecker and Danny Reinberg and Karim-Jean Armache},

title = {Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2},

journal = {Molecular Cell},

year = {2018},

volume = {70},

publisher = {Elsevier},

month = {may},

url = {https://doi.org/10.1016/j.molcel.2018.03.019},

number = {3},

pages = {435--44800000},

doi = {10.1016/j.molcel.2018.03.019}

}

MLA

Cite this

MLA Copy

Lee, Chul Hwan, et al. “Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2.” Molecular Cell, vol. 70, no. 3, May. 2018, pp. 435-44800000. https://doi.org/10.1016/j.molcel.2018.03.019.

Publisher

Elsevier

Journal

Molecular Cell

scimago Q1

wos Q1

SJR

9.051

CiteScore

24.4

Impact factor

16.6

ISSN

10972765 (Print)

10974164 (Electronic)