DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters

被引:746
作者
Robertson, KD [1 ]
Ait-Si-Ali, S [1 ]
Yokochi, T [1 ]
Wade, PA [1 ]
Jones, PL [1 ]
Wolffe, AP [1 ]
机构
[1] NICHD, Mol Embryol Lab, NIH, Bethesda, MD USA
关键词
D O I
10.1038/77124
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Methylation of CpG islands is associated with transcriptional silencing and the formation of nuclease-resistant chromatin structures enriched in hypoacetylated histones(1-3). Methyl-CpG-binding proteins, such as MeCP2, provide a link between methylated DNA and hypoacetylated histones by recruiting histone deacetylase(4,5), but the mechanisms establishing the methylation patterns themselves are unknown. Whether DNA methylation is always causal for the assembly of repressive chromatin or whether features of transcriptionally silent chromatin might target methyltransferase remains unresolved. Mammalian DNA methyltransferases show little sequence specificity in vitro, yet methylation can be targeted in vivo within chromosomes to repetitive elements(6,7), centromeress(8-10) and imprinted loci(11). This targeting is frequently disrupted in tumour cells, resulting in the improper silencing of tumour-suppressor genes associated with CpG islands(1,2). Here we show that the predominant mammalian DNA methyltransferase, DNMT1, co-purifies with the retinoblastoma (Rb) tumour suppressor gene product, E2F1. and HDAC1 and that DNMT1 cooperates with Rb to repress transcription from promoters containing E2F-binding sites. These results establish a link between DNA methylation, histone deacetylase and sequence-specific DNA binding activity, as well as a growth-regulatory pathway that is disrupted in nearly all cancer cells.
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页码:338 / 342
页数:5
相关论文
共 28 条
  • [1] Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A
    Ait-Si-Ali, S
    Ramirez, S
    Barre, FX
    Dkhissi, F
    Magnaghi-Jaulin, L
    Girault, JA
    Robin, P
    Knibiehler, M
    Pritchard, LL
    Ducommun, B
    Trouche, D
    Harel-Bellan, A
    [J]. NATURE, 1998, 396 (6707) : 184 - 186
  • [2] Human DNA (cytosine-5) methyltransferase PCNA complex as a target for p21(WAF1)
    Chuang, LSH
    Ian, HI
    Koh, TW
    Ng, HH
    Xu, GL
    Li, BFL
    [J]. SCIENCE, 1997, 277 (5334) : 1996 - 2000
  • [3] THE RETINOBLASTOMA PROTEIN AND BRG1 FORM A COMPLEX AND COOPERATE TO INDUCE CELL-CYCLE ARREST
    DUNAIEF, JL
    STROBER, BE
    GUHA, S
    KHAVARI, PA
    ALIN, K
    LUBAN, J
    BEGEMANN, M
    CRABTREE, GR
    GOFF, SP
    [J]. CELL, 1994, 79 (01) : 119 - 130
  • [4] DNA methylation models histone acetylation
    Eden, S
    Hashimshony, T
    Keshet, I
    Cedar, H
    Thorne, AW
    [J]. NATURE, 1998, 394 (6696) : 842 - 842
  • [5] DNA methyltransferase Dnmt1 associates with histone deacetylase activity
    Fuks, F
    Burgers, WA
    Brehm, A
    Hughes-Davies, L
    Kouzarides, T
    [J]. NATURE GENETICS, 2000, 24 (01) : 88 - 91
  • [6] Repeat-induced gene silencing in mammals
    Garrick, D
    Fiering, S
    Martin, DIK
    Whitelaw, E
    [J]. NATURE GENETICS, 1998, 18 (01) : 56 - 59
  • [7] Role of the retinoblastoma protein family, pRB, p107 and p130 in the negative control of cell growth
    Graña, X
    Garriga, J
    Mayol, X
    [J]. ONCOGENE, 1998, 17 (25) : 3365 - 3383
  • [8] The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome
    Hansen, RS
    Wijmenga, C
    Luo, P
    Stanek, AM
    Canfield, TK
    Weemaes, CMR
    Gartler, SM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (25) : 14412 - 14417
  • [9] Drosophila proteins related to vertebrate DNA (5-cytosine) methyltransferases
    Hung, MS
    Karthikeyan, N
    Huang, BL
    Koo, HC
    Kiger, J
    Shen, CKJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (21) : 11940 - 11945
  • [10] ISSA JP, 1997, LEUKEMIA S1, V11, P7