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

被引:441
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
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