Mechanisms of Polycomb gene silencing: knowns and unknowns

被引:1083
作者
Simon, Jeffrey A. [1 ]
Kingston, Robert E. [2 ,3 ]
机构
[1] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA
[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
关键词
RNA-POLYMERASE-II; HISTONE METHYLTRANSFERASE ACTIVITY; EMBRYONIC STEM-CELLS; POLYCOMB/TRITHORAX RESPONSE ELEMENTS; TRITHORAX GROUP PROTEINS; DROSOPHILA-MELANOGASTER; BITHORAX COMPLEX; HOMEOTIC GENE; H2A UBIQUITINATION; STRUCTURAL BASIS;
D O I
10.1038/nrm2763
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Polycomb proteins form chromatin-modifying complexes that implement transcriptional silencing in higher eukaryotes. Hundreds of genes are silenced by Polycomb proteins, including dozens of genes that encode crucial developmental regulators in organisms ranging from plants to humans. Two main families of complexes, called Polycomb repressive complex 1 (PRC1) and PRC2, are targeted to repressed regions. Recent studies have advanced our understanding of these complexes, including their potential mechanisms of gene silencing, the roles of chromatin modifications, their means of delivery to target genes and the functional distinctions among variant complexes. Emerging concepts include the existence of a Polycomb barrier to transcription elongation and the involvement of non-coding RNAs in the targeting of Polycomb complexes. These findings have an impact on the epigenetic programming of gene expression in many biological systems.
引用
收藏
页码:697 / 708
页数:12
相关论文
共 171 条
  • [1] The Drosophila BRM complex facilitates global transcription by RNA polymerase II
    Armstrong, JA
    Papoulas, O
    Daubresse, G
    Sperling, AS
    Lis, JT
    Scott, MP
    Tamkun, JW
    [J]. EMBO JOURNAL, 2002, 21 (19) : 5245 - 5254
  • [2] Genomic biology - The epigenomic era opens
    Baylin, Stephen B.
    Schuebel, Kornel E.
    [J]. NATURE, 2007, 448 (7153) : 548 - 549
  • [3] An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors
    Ben-Porath, Ittai
    Thomson, Matthew W.
    Carey, Vincent J.
    Ge, Ruping
    Bell, George W.
    Regev, Aviv
    Weinberg, Robert A.
    [J]. NATURE GENETICS, 2008, 40 (05) : 499 - 507
  • [4] The MES-2/MES-3/MES-6 complex and regulation of histone H3 methylation in C-elegans
    Bender, LB
    Cao, R
    Zhang, Y
    Strome, S
    [J]. CURRENT BIOLOGY, 2004, 14 (18) : 1639 - 1643
  • [5] A bivalent chromatin structure marks key developmental genes in embryonic stem cells
    Bernstein, BE
    Mikkelsen, TS
    Xie, XH
    Kamal, M
    Huebert, DJ
    Cuff, J
    Fry, B
    Meissner, A
    Wernig, M
    Plath, K
    Jaenisch, R
    Wagschal, A
    Feil, R
    Schreiber, SL
    Lander, ES
    [J]. CELL, 2006, 125 (02) : 315 - 326
  • [6] Nucleosomes can form a polar barrier to transcript elongation by RNA polymerase II
    Bondarenko, Vladimir A.
    Steele, Louise M.
    Ujvari, Andrea
    Gaykalova, Daria A.
    Kulaeva, Olga I.
    Polikanov, Yury S.
    Luse, Donal S.
    Studitsky, Vasily M.
    [J]. MOLECULAR CELL, 2006, 24 (03) : 469 - 479
  • [7] Polycomb complexes repress developmental regulators in murine embryonic stem cells
    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
    [J]. NATURE, 2006, 441 (7091) : 349 - 353
  • [8] The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
    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
    [J]. GENES & DEVELOPMENT, 2007, 21 (05) : 525 - 530
  • [9] Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions
    Bracken, AP
    Dietrich, N
    Pasini, D
    Hansen, KH
    Helin, K
    [J]. GENES & DEVELOPMENT, 2006, 20 (09) : 1123 - 1136
  • [10] EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer
    Adrian P. Bracken
    Diego Pasini
    Maria Capra
    Elena Prosperini
    Elena Colli
    Kristian Helin
    [J]. The EMBO Journal, 2003, 22 (20) : 5323 - 5335