Ring1B Compacts Chromatin Structure and Represses Gene Expression Independent of Histone Ubiquitination

被引:437
作者
Eskeland, Ragnhild [1 ]
Leeb, Martin [2 ]
Grimes, Graeme R. [1 ]
Kress, Clemence [1 ]
Boyle, Shelagh [1 ]
Sproul, Duncan [3 ]
Gilbert, Nick [3 ]
Fan, Yuhong [4 ]
Skoultchi, Arthur I. [4 ]
Wutz, Anton [2 ]
Bickmore, Wendy A. [1 ]
机构
[1] Univ Edinburgh, Inst Genet & Mol Med, Human Genet Unit, MRC, Edinburgh EH4 2XU, Midlothian, Scotland
[2] Res Inst Mol Pathol, A-1030 Vienna, Austria
[3] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh Canc Res Ctr, Edinburgh EH4 2XR, Midlothian, Scotland
[4] Dept Cell Biol, Albert Einstein Coll Med, Bronx, NY 10461 USA
基金
英国惠康基金; 英国医学研究理事会;
关键词
EMBRYONIC STEM-CELLS; POLYCOMB GROUP PROTEINS; H3; LYSINE-27; METHYLATION; RNA-POLYMERASE-II; NUCLEAR REORGANIZATION; X-INACTIVATION; DEVELOPMENTAL REGULATORS; BITHORAX COMPLEX; IN-VIVO; TRANSCRIPTION;
D O I
10.1016/j.molcel.2010.02.032
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
How polycomb group proteins repress gene expression in vivo is not known. While histone-modifying activities of the polycomb repressive complexes (PRCs) have been studied extensively, in vitro data have suggested a direct activity of the PRC1 complex in compacting chromatin. Here, we investigate higher-order chromatin compaction of polycomb targets in vivo. We show that PRCs are required to maintain a compact chromatin state at Hox loci in embryonic stem cells (ESCs). There is specific decompaction in the absence of PRC2 or PRC1. This is due to a PRC1 -like complex, since decompaction occurs in Ring 1B null cells that still have PRC2mediated H3K27 methylation. Moreover, we show that the ability of Ring1B to restore a compact chromatin state and to repress Hox gene expression is not dependent on its histone ubiquitination activity. We suggest that Ring1B-mediated chromatin compaction acts to directly limit transcription in vivo.
引用
收藏
页码:452 / 464
页数:13
相关论文
共 58 条
  • [1] REGULATION OF THE HIGHER-ORDER STRUCTURE OF CHROMATIN BY HISTONES-H1 AND HISTONES-H5
    ALLAN, J
    COWLING, GJ
    HARBORNE, N
    CATTINI, P
    CRAIGIE, R
    GOULD, H
    [J]. JOURNAL OF CELL BIOLOGY, 1981, 90 (02) : 279 - 288
  • [2] Chromatin signatures of pluripotent cell lines
    Azuara, V
    Perry, P
    Sauer, S
    Spivakov, M
    Jorgensen, HF
    John, RM
    Gouti, M
    Casanova, M
    Warnes, G
    Merkenschlager, M
    Fisher, AG
    [J]. NATURE CELL BIOLOGY, 2006, 8 (05) : 532 - U189
  • [3] Bel-Vialar S, 2002, DEVELOPMENT, V129, P5103
  • [4] 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
  • [5] 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
  • [6] 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
  • [7] General transcription factors bind promoters repressed by Polycomb group proteins
    Breiling, A
    Turner, BM
    Bianchi, ME
    Orlando, V
    [J]. NATURE, 2001, 412 (6847) : 651 - 655
  • [8] Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1b
    Buchwald, Gretel
    van der Stoop, Petra
    Weichenrieder, Oliver
    Perrakis, Anastassis
    van Lohuizen, Maarten
    Sixma, Titia K.
    [J]. EMBO JOURNAL, 2006, 25 (11) : 2465 - 2474
  • [9] 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
  • [10] Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency
    Chamberlain, Stormy J.
    Yee, Della
    Magnuson, Terry
    [J]. STEM CELLS, 2008, 26 (06) : 1496 - 1505