Maintaining cell identity: PRC2-mediated regulation of transcription and cancer

被引:329
作者
Comet, Itys [1 ,2 ]
Riising, Eva M. [4 ]
Leblanc, Benjamin [1 ,2 ,3 ]
Helin, Kristian [1 ,2 ,3 ]
机构
[1] Univ Copenhagen, BRIC, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark
[2] Univ Copenhagen, Ctr Epigenet, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark
[3] Univ Copenhagen, Fac Hlth & Med Sci, Danish Stem Cell Ctr Danstem, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
[4] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England
基金
新加坡国家研究基金会; 欧洲研究理事会; 欧盟第七框架计划; 英国医学研究理事会;
关键词
REPRESSIVE COMPLEX 2; HISTONE METHYLTRANSFERASE EZH2; POLYCOMB GROUP PROTEINS; EPITHELIAL-MESENCHYMAL TRANSITION; SOMATIC MUTATIONS; STEM-CELLS; GENE EZH2; DEVELOPMENTAL REGULATORS; MYELODYSPLASTIC SYNDROME; SELECTIVE-INHIBITION;
D O I
10.1038/nrc.2016.83
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb repressive complex 2 (PRC2), has attracted broad research attention in the past few years because of its involvement in the development and maintenance of many types of cancer and the use of specific EZH2 inhibitors in clinical trials. Several observations show that PRC2 can have both oncogenic and tumour-suppressive functions. We propose that these apparently opposing roles of PRC2 in cancer are a consequence of the molecular function of the complex in maintaining, rather than specifying, the transcriptional repression state of its several thousand target genes.
引用
收藏
页码:803 / 810
页数:8
相关论文
共 122 条
  • [1] The ASXL-BAP1 axis: new factors in myelopoiesis, cancer and epigenetics
    Abdel-Wahab, O.
    Dey, A.
    [J]. LEUKEMIA, 2013, 27 (01) : 10 - 15
  • [2] ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression
    Abdel-Wahab, Omar
    Adli, Mazhar
    LaFave, Lindsay M.
    Gao, Jie
    Hricik, Todd
    Shih, Alan H.
    Pandey, Suveg
    Patel, Jay P.
    Chung, Young Rock
    Koche, Richard
    Perna, Fabiana
    Zhao, Xinyang
    Taylor, Jordan E.
    Park, Christopher Y.
    Carroll, Martin
    Melnick, Ari
    Nimer, Stephen D.
    Jaffe, Jacob D.
    Aifantis, Iannis
    Bernstein, Bradley E.
    Levine, Ross L.
    [J]. CANCER CELL, 2012, 22 (02) : 180 - 193
  • [3] H3K36me3 key to Polycomb-mediated gene silencing in lineage specification
    Abed, Jumana AlHaj
    Jones, Richard S.
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (12) : 1214 - 1215
  • [4] AKAM M, 1987, DEVELOPMENT, V101, P1
  • [5] Three-dimensional culture sensitizes epithelial ovarian cancer cells to EZH2 methyltransferase inhibition
    Amatangelo, Michael D.
    Garipov, Azat
    Li, Hua
    Conejo-Garcia, Jose R.
    Speicher, David W.
    Zhang, Rugang
    [J]. CELL CYCLE, 2013, 12 (13) : 2113 - 2119
  • [6] EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation
    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.
    [J]. CANCER CELL, 2013, 23 (05) : 677 - 692
  • [7] Silencing chromatin: comparing modes and mechanisms
    Beisel, Christian
    Paro, Renato
    [J]. NATURE REVIEWS GENETICS, 2011, 12 (02) : 123 - 135
  • [8] Reduced H3K27me3 and DNA Hypomethylation Are Major Drivers of Gene Expression in K27M Mutant Pediatric High-Grade Gliomas
    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.
    [J]. CANCER CELL, 2013, 24 (05) : 660 - 672
  • [9] A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis
    Berg, Tobias
    Thoene, Silvia
    Yap, Damian
    Wee, Tracee
    Schoeler, Nathalie
    Rosten, Patty
    Lim, Emilia
    Bilenky, Misha
    Mungall, Andrew J.
    Oellerich, Thomas
    Lee, Sherry
    Lai, Courteney K.
    Umlandt, Patricia
    Salmi, Anisa
    Chang, Harry
    Yue, Lisa
    Lai, David
    Cheng, S-W Grace
    Morin, Ryan D.
    Hirst, Martin
    Serve, Hubert
    Marra, Marco A.
    Morin, Gregg B.
    Gascoyne, Randy D.
    Aparicio, Samuel A.
    Humphries, R. Keith
    [J]. BLOOD, 2014, 123 (25) : 3914 - 3924
  • [10] Targeting Polycomb systems to regulate gene expression: modifications to a complex story
    Blackledge, Neil P.
    Rose, Nathan R.
    Klose, Robert J.
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2015, 16 (11) : 643 - 649