DNA methylation and complete transcriptional silencing of cancer genes persist after depletion of EZH2

被引:89
作者
McGarvey, Kelly M.
Greene, Eriko
Fahrner, Jill A.
Jenuwein, Thomas
Baylin, Stephen B.
机构
[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Sch Med, Grad Program Cellular & Mol Med, Baltimore, MD 21231 USA
[3] Vienna Bioctr, Res Inst Mol Pathol, Vienna, Austria
关键词
D O I
10.1158/0008-5472.CAN-06-2029
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recent work suggests a link between the polycomb group protein EZH2 and mediation of gene silencing in association with maintenance of DNA methylation. However, we show that whereas basally expressed target cancer genes with minimal DNA methylation have increased transcription during EZH2 knockdown, densely DNA hypermethylated and silenced genes retain their methylation and remain transcriptionally silent. These results suggest that EZH2 can modulate transcription of basally expressed genes but not silent genes that are densely DNA methylated.
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页码:5097 / 5102
页数:6
相关论文
共 19 条
  • [1] Dominant-negative histone H3 lysine 27 mutant derepresses silenced tumor suppressor genes and reverses the drug-resistant phenotype in cancer cells
    Abbosh, Phillip H.
    Montgomery, John S.
    Starkey, Jason A.
    Novotny, Milos
    Zuhowski, Eleanor G.
    Egorin, Merrill J.
    Moseman, Annie P.
    Golas, Adam
    Brannon, Kate M.
    Balch, Curtis
    Huang, Tim H. M.
    Nephew, Kenneth P.
    [J]. CANCER RESEARCH, 2006, 66 (11) : 5582 - 5591
  • [2] Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene
    Bachman, KE
    Park, BH
    Rhee, I
    Rajagopalan, H
    Herman, JG
    Baylin, SB
    Kinzler, KW
    Vogelstein, B
    [J]. CANCER CELL, 2003, 3 (01) : 89 - 95
  • [3] 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
  • [4] 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
  • [5] The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3
    Cao, R
    Zhang, Y
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 2004, 14 (02) : 155 - 164
  • [6] Role of histone H3 lysine 27 methylation in polycomb-group silencing
    Cao, R
    Wang, LJ
    Wang, HB
    Xia, L
    Erdjument-Bromage, H
    Tempst, P
    Jones, RS
    Zhang, Y
    [J]. SCIENCE, 2002, 298 (5595) : 1039 - 1043
  • [7] Fahrner JA, 2002, CANCER RES, V62, P7213
  • [8] A GENOMIC SEQUENCING PROTOCOL THAT YIELDS A POSITIVE DISPLAY OF 5-METHYLCYTOSINE RESIDUES IN INDIVIDUAL DNA STRANDS
    FROMMER, M
    MCDONALD, LE
    MILLAR, DS
    COLLIS, CM
    WATT, F
    GRIGG, GW
    MOLLOY, PL
    PAUL, CL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (05) : 1827 - 1831
  • [9] Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27
    Kirmizis, A
    Bartley, SM
    Kuzmichev, A
    Margueron, R
    Reinberg, D
    Green, R
    Farnham, PJ
    [J]. GENES & DEVELOPMENT, 2004, 18 (13) : 1592 - 1605
  • [10] EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells
    Kleer, CG
    Cao, Q
    Varambally, S
    Shen, RL
    Ota, L
    Tomlins, SA
    Ghosh, D
    Sewalt, RGAB
    Otte, AP
    Hayes, DF
    Sabel, MS
    Livant, D
    Weiss, SJ
    Rubin, MA
    Chinnaiyan, AM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (20) : 11606 - 11611