PRC2 mediated H3K27 methylations in cellular identity and cancer

被引：166

作者：

Conway, Eric ^{[1
]}

Healy, Evan ^{[1
]}

Bracken, Adrian P. ^{[1
]}

机构：

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

来源：

CURRENT OPINION IN CELL BIOLOGY | 2015年 / 37卷

关键词：

REPRESSIVE COMPLEX 2; EMBRYONIC STEM-CELLS; SOMATIC MUTATIONS; HISTONE H3; CPG ISLANDS; DEVELOPMENTAL REGULATORS; EZH2; MUTATIONS; K27M MUTATION; POLYCOMB; PROTEINS;

D O I：

10.1016/j.ceb.2015.10.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The Polycomb Repressive Complex 2 (PRC2) is a multiprotein chromatin modifying complex that is essential for vertebrate development and differentiation. It is composed of a trimeric core of SUZ12, EED and EZH1/2 and is responsible for catalysing both di-methylation and tri-methylation of Histone H3 at lysine 27 (H3K27me2/3). Both H3K27 methylations contribute to the role of PRC2 in maintaining cellular identity. In all cell types, the H3K27me3 modification is associated with repression of genes encoding regulators of alternative lineages. The less well-characterised H3K27me2 modification is ubiquitous throughout the genome and is thought to act like a protective blanket to maintain the repression of non-H3K27me3 associated genes and cell-type-specific enhancers of alternative lineages. Recent cancer genome sequencing studies highlighted that several genes encoding PRC2 components as well as Histone H3 are mutated in multiple cancer types. Intriguingly, these cancers have changes in the global levels of the H3K27me2 and H3K27me3 modifications as well as genome-wide redistributions. Exciting new studies suggest that these changes confer context dependent blocks in cellular differentiation and increased vulnerability to aberrant cancer signalling pathways.

引用

页码：42 / 48

页数：7

共 63 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]

Epigenetic reprogramming by tumor-derived EZH2 gain-of-function mutations promotes aggressive 3D cell morphologies and enhances melanoma tumor growth [J].

Barsotti, Anthony M. ;

Ryskin, Michael ;

Zhong, Wenyan ;

Zhang, Wei-Guo ;

Giannakou, Andreas ;

Loreth, Christine ;

Diesl, Veronica ;

Follettie, Maximillian ;

Golas, Jonathon ;

Lee, Michelle ;

Nichols, Timothy ;

Fan, Conglin ;

Li, Gang ;

Dann, Stephen ;

Fantin, Valeria R. ;

Arndt, Kim ;

Verhelle, Dominique ;

Rollins, Robert A. .

ONCOTARGET, 2015, 6 (05) :2928-2938

[3]

Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia [J].

Beekman, Renee ;

Valkhof, Marijke G. ;

Sanders, Mathijs A. ;

van Strien, Paulette M. H. ;

Haanstra, Jurgen R. ;

Broeders, Lianne ;

Geertsma-Kleinekoort, Wendy M. ;

Veerman, Anjo J. P. ;

Valk, Peter J. M. ;

Verhaak, Roel G. ;

Lowenberg, Bob ;

Touw, Ivo P. .

BLOOD, 2012, 119 (22) :5071-5077

[4]

EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation [J].

Beguelin, Wendy ;

Popovic, Relja ;

Teater, Matt ;

Jiang, Yanwen ;

Bunting, Karen L. ;

Rosen, Monica ;

Shen, Hao ;

Yang, Shao Ning ;

Wang, Ling ;

Ezponda, Teresa ;

Martinez-Garcia, Eva ;

Zhang, Haikuo ;

Zheng, Yupeng ;

Verma, Sharad K. ;

McCabe, Michael T. ;

Ott, Heidi M. ;

Van Aller, Glenn S. ;

Kruger, Ryan G. ;

Liu, Yan ;

McHugh, Charles F. ;

Scott, David W. ;

Chung, Young Rock ;

Kelleher, Neil ;

Shaknovich, Rita ;

Creasy, Caretha L. ;

Gascoyne, Randy D. ;

Wong, Kwok-Kin ;

Cerchietti, Leandro ;

Levine, Ross L. ;

Abdel-Wahab, Omar ;

Licht, Jonathan D. ;

Elemento, Olivier ;

Melnick, Ari M. .

CANCER CELL, 2013, 23 (05) :677-692

[5]

Reduced H3K27me3 and DNA Hypomethylation Are Major Drivers of Gene Expression in K27M Mutant Pediatric High-Grade Gliomas [J].

Bender, Sebastian ;

Tang, Yujie ;

Lindroth, Anders M. ;

Hovestadt, Volker ;

Jones, David T. W. ;

Kool, Marcel ;

Zapatka, Marc ;

Northcott, Paul A. ;

Sturm, Dominik ;

Wang, Wei ;

Radlwimmer, Bernhard ;

Hojfeldt, Jonas W. ;

Truffaux, Nathalene ;

Castel, David ;

Schubert, Simone ;

Ryzhova, Marina ;

Seker-Cin, Huriye ;

Gronych, Jan ;

Johann, Pascal David ;

Stark, Sebastian ;

Meyer, Jochen ;

Milde, Till ;

Schuhmann, Martin ;

Ebinger, Martin ;

Monoranu, Camelia-Maria ;

Ponnuswami, Anitha ;

Chen, Spenser ;

Jones, Chris ;

Witt, Olaf ;

Collins, V. Peter ;

von Deimling, Andreas ;

Jabado, Nada ;

Puget, Stephanie ;

Grill, Jacques ;

Helin, Kristian ;

Korshunov, Andrey ;

Lichter, Peter ;

Monje, Michelle ;

Plass, Christoph ;

Cho, Yoon-Jae ;

Pfister, Stefan M. .

CANCER CELL, 2013, 24 (05) :660-672

[6]

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

[7]

EZH2 mutations are frequent and represent an early event in follicular lymphoma [J].

Boedoer, Csaba ;

Grossmann, Vera ;

Popov, Nikolay ;

Okosun, Jessica ;

O'Riain, Ciaran ;

Tan, King ;

Marzec, Jacek ;

Araf, Shamzah ;

Wang, Jun ;

Lee, Abigail M. ;

Clear, Andrew ;

Montoto, Silvia ;

Matthews, Janet ;

Iqbal, Sameena ;

Rajnai, Hajnalka ;

Rosenwald, Andreas ;

Ott, German ;

Campo, Elias ;

Rimsza, Lisa M. ;

Smeland, Erlend B. ;

Chan, Wing C. ;

Braziel, Rita M. ;

Staudt, Louis M. ;

Wright, George ;

Lister, T. Andrew ;

Elemento, Olivier ;

Hills, Robert ;

Gribben, John G. ;

Chelala, Claude ;

Matolcsy, Andras ;

Kohlmann, Alexander ;

Haferlach, Torsten ;

Gascoyne, Randy D. ;

Fitzgibbon, Jude .

BLOOD, 2013, 122 (18) :3165-3168

[8]

Polycomb complexes repress developmental regulators in murine embryonic stem cells [J].

Boyer, LA ;

Plath, K ;

Zeitlinger, J ;

Brambrink, T ;

Medeiros, LA ;

Lee, TI ;

Levine, SS ;

Wernig, M ;

Tajonar, A ;

Ray, MK ;

Bell, GW ;

Otte, AP ;

Vidal, M ;

Gifford, DK ;

Young, RA ;

Jaenisch, R .

NATURE, 2006, 441 (7091) :349-353

[9]

The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells [J].

Bracken, Adrian P. ;

Kleine-Kohlbrecher, Daniela ;

Dietrich, Nikolaj ;

Pasini, Diego ;

Gargiulo, Gaetano ;

Beekman, Chantal ;

Theilgaard-Monch, Kim ;

Minucci, Saverio ;

Porse, Bo T. ;

Marine, Jean-Christophe ;

Hansen, Klaus H. ;

Helin, Kristian .

GENES & DEVELOPMENT, 2007, 21 (05) :525-530

[10]

Polycomb group proteins: navigators of lineage pathways led astray in cancer [J].

Bracken, Adrian P. ;

Helin, Kristian .

NATURE REVIEWS CANCER, 2009, 9 (11) :773-784

← 1 2 3 4 5 6 7 →