PRC2.1 and PRC2.2 Synergize to Coordinate H3K27 Trimethylation

被引：128

作者：

Healy, Evan ^{[1
]}

Mucha, Marlena ^{[1
]}

Glancy, Eleanor ^{[1
]}

Fitzpatrick, Darren J. ^{[1
]}

Conway, Eric ^{[1
]}

Neikes, Hannah K. ^{[1
]}

Monger, Craig ^{[1
]}

Van Mierlo, Guido ^{[2
]}

Baltissen, Marijke P. ^{[2
]}

Koseki, Yoko ^{[3
]}

Vermeulen, Michiel ^{[2
]}

Koseki, Haruhiko ^{[3
]}

Bracken, Adrian P. ^{[1
]}

机构：

[1] Trinity Coll Dublin, Smurfit Inst Genet, Dublin 2, Ireland

[2] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Fac Sci, Dept Mol Biol, Nijmegen, Netherlands

[3] RIKEN, Ctr Integrat Med Sci, IMS, Lab Dev Genet, Yokohama, Kanagawa, Japan

来源：

MOLECULAR CELL | 2019年 / 76卷 / 03期

基金：

爱尔兰科学基金会;

关键词：

HISTONE H3; CELL IDENTITY; POLYCOMB; COMPLEX; PRC1; EZH2; CHROMATIN; METHYLATION; PROTEIN; JARID2;

D O I：

10.1016/j.molcel.2019.08.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Polycomb repressive complex 2 (PRC2) is composed of EED, SUZ12, and EZH1/2 and mediates mono-, di-, and trimethylation of histone H3 at lysine 27. At least two independent subcomplexes exist, defined by their specific accessory proteins: PRC2.1 (PCL1-3, EPOP, and PALI1/2) and PRC2.2 (AEBP2 and JARID2). We show that PRC2.1 and PRC2.2 share the majority of target genes in mouse embryonic stem cells. The loss of PCL1-3 is sufficient to evict PRC2.1 from Polycomb target genes but only leads to a partial reduction of PRC2.2 and H3K27me3. Conversely, disruption of PRC2.2 function through the loss of either JARID2 or RING1A/B is insufficient to completely disrupt targeting of SUZ12 by PCLs. Instead, the combined loss of both PRC2.1 and PRC2.2 is required, leading to the global mislocalization of SUZ12. This supports a model in which the specific accessory proteins within PRC2.1 and PRC2.2 cooperate to direct H3K27me3 via both synergistic and independent mechanisms.

引用

页码：437 / +

页数：22

共 85 条

[1] Two distinct modes for propagation of histone PTMs across the cell cycle [J].

Alabert, Constance ;

Barth, Teresa K. ;

Reveron-Gomez, Nazaret ;

Sidoli, Simone ;

Schmidt, Andreas ;

Jensen, Ole N. ;

Imhof, Axel ;

Groth, Anja .

GENES & DEVELOPMENT, 2015, 29 (06) :585-590

[2] Reciprocal interactions of human C10orf12 and C17orf96 with PRC2 revealed by BioTAP-XL cross-linking and affinity purification [J].

Alekseyenko, Artyom A. ;

Gorchakov, Andrey A. ;

Kharchenko, Peter V. ;

Kuroda, Mitzi I. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (07) :2488-2493

[3]

[Anonymous], F1000 RES, DOI DOI 10.12688/F1000RESEARCH.7563.2

[4] Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors [J].

Baker, Theresa ;

Nerle, Sujata ;

Pritchard, Justin ;

Zhao, Boyang ;

Rivera, Victor M. ;

Garner, Andrew ;

Gonzalvez, Francois .

ONCOTARGET, 2015, 6 (32) :32646-32655

[5] Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity [J].

Ballare, Cecilia ;

Lange, Martin ;

Lapinaite, Audrone ;

Martin, Gloria Mas ;

Morey, Lluis ;

Pascual, Gloria ;

Liefke, Robert ;

Simon, Bernd ;

Shi, Yang ;

Gozani, Or ;

Carlomagno, Teresa ;

Aznar Benitah, Salvador ;

Di Croce, Luciano .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (12) :1257-+

[6] EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells [J].

Beringer, Malte ;

Pisano, Paola ;

Di Carlo, Valerio ;

Blanco, Enrique ;

Chammas, Paul ;

Vizan, Pedro ;

Gutierrez, Arantxa ;

Aranda, Sergi ;

Payer, Bernhard ;

Wierer, Michael ;

Di Croce, Luciano .

MOLECULAR CELL, 2016, 64 (04) :645-658

[7] Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation [J].

Blackledge, Neil P. ;

Farcas, Anca M. ;

Kondo, Takashi ;

King, Hamish W. ;

McGouran, Joanna F. ;

Hanssen, Lars L. P. ;

Ito, Shinsuke ;

Cooper, Sarah ;

Kondo, Kaori ;

Koseki, Yoko ;

Ishikura, Tomoyuki ;

Long, Hannah K. ;

Sheahan, Thomas W. p ;

Brockdorff, Neil ;

Kessler, Benedikt M. ;

Koseki, Haruhiko ;

Klose, Robert J. .

CELL, 2014, 157 (06) :1445-1459

[8] Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer [J].

Bracken, Adrian P. ;

Brien, Gerard L. ;

Verrijzer, C. Peter .

GENES & DEVELOPMENT, 2019, 33 (15-16) :936-959

[9] Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions [J].

Bracken, AP ;

Dietrich, N ;

Pasini, D ;

Hansen, KH ;

Helin, K .

GENES & DEVELOPMENT, 2006, 20 (09) :1123-1136

[10] EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer [J].

Adrian P. Bracken ;

Diego Pasini ;

Maria Capra ;

Elena Prosperini ;

Elena Colli ;

Kristian Helin .

The EMBO Journal, 2003, 22 (20) :5323-5335

← 1 2 3 4 5 6 7 8 9 →