KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

被引:345
作者
Farcas, Anca M. [1 ]
Blackledge, Neil P. [1 ]
Sudbery, Ian [2 ]
Long, Hannah K. [1 ,3 ]
McGouran, Joanna F. [4 ]
Rose, Nathan R. [1 ]
Lee, Sheena [5 ]
Sims, David [2 ]
Cerase, Andrea [1 ]
Sheahan, Thomas W. [1 ]
Koseki, Haruhiko [6 ]
Brockdorff, Neil [1 ]
Ponting, Chris P. [2 ]
Kessler, Benedikt M. [4 ]
Klose, Robert J. [1 ]
机构
[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
[2] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, CGAT, Oxford, England
[3] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Haematol Unit, Oxford OX3 9DU, England
[4] Univ Oxford, Nuffield Dept Clin Med, Ctr Cellular & Mol Physiol, Cent Prote Facil,Ubiquitin Proteolysis Grp, Oxford, England
[5] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England
[6] RIKEN Res Ctr Allergy & Immunol, Lab Dev Genet, Yokohama, Kanagawa, Japan
基金
英国医学研究理事会; 英国惠康基金;
关键词
EMBRYONIC STEM-CELLS; HISTONE METHYLTRANSFERASE ACTIVITY; GROUP PROTEINS RING1A/B; BINDING-PROTEIN; CHROMATIN-STRUCTURE; X-INACTIVATION; TRANSCRIPTIONAL REPRESSOR; DEVELOPMENTAL REGULATORS; H2A UBIQUITYLATION; EPIGENETIC MEMORY;
D O I
10.7554/eLife.00205
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
CpG islands (CGIs) are associated with most mammalian gene promoters. A subset of CGIs act as polycomb response elements (PREs) and are recognized by the polycomb silencing systems to regulate expression of genes involved in early development. How CGIs function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that KDM2B (FBXL10) specifically recognizes non-methylated DNA in CGIs and recruits the polycomb repressive complex 1 (PRC1). This contributes to histone H2A lysine 119 ubiquitylation (H2AK119ub1) and gene repression. Unexpectedly, we also find that CGIs are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CGI-associated genes for susceptibility to polycomb-mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CGIs by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CGIs as mammalian PREs.
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页数:26
相关论文
共 85 条
[71]   Mechanisms of Polycomb gene silencing: knowns and unknowns [J].
Simon, Jeffrey A. ;
Kingston, Robert E. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (10) :697-708
[72]  
Smyth GK., 2004, Statistical Applications in Genetics and Molecular Biology, P3, DOI [10.2202/1544-6115.1027, DOI 10.2202/1544-6115.1027]
[73]   Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression [J].
Strahl, BD ;
Grant, PA ;
Briggs, SD ;
Sun, ZW ;
Bone, JR ;
Caldwell, JA ;
Mollah, S ;
Cook, RG ;
Shabanowitz, J ;
Hunt, DF ;
Allis, CD .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (05) :1298-1306
[74]   RYBP-PRC1 Complexes Mediate H2A Ubiquitylation at Polycomb Target Sites Independently of PRC2 and H3K27me3 [J].
Tavares, Ligia ;
Dimitrova, Emilia ;
Oxley, David ;
Webster, Judith ;
Poot, Raymond ;
Demmers, Jeroen ;
Bezstarosti, Karel ;
Taylor, Stephen ;
Ura, Hiroki ;
Koide, Hiroshi ;
Wutz, Anton ;
Vidal, Miguel ;
Elderkin, Sarah ;
Brockdorff, Neil .
CELL, 2012, 148 (04) :664-678
[75]   CpG islands influence chromatin structure via the CpG-binding protein Cfp1 [J].
Thomson, John P. ;
Skene, Peter J. ;
Selfridge, Jim ;
Clouaire, Thomas ;
Guy, Jacky ;
Webb, Shaun ;
Kerr, Alastair R. W. ;
Deaton, Aimee ;
Andrews, Rob ;
James, Keith D. ;
Turner, Daniel J. ;
Illingworth, Robert ;
Bird, Adrian .
NATURE, 2010, 464 (7291) :1082-U162
[76]  
VASSILEV AP, 1995, J CELL SCI, V108, P1205
[77]   Role of histone H2A ubiquitination in polycomb silencing [J].
Wang, HB ;
Wang, LJ ;
Erdjument-Bromage, H ;
Vidal, M ;
Tempst, P ;
Jones, RS ;
Zhang, Y .
NATURE, 2004, 431 (7010) :873-878
[78]   Hierarchical recruitment of Polycomb group silencing complexes [J].
Wang, L ;
Brown, JL ;
Cao, R ;
Zhang, Y ;
Kassis, JA ;
Jones, RS .
MOLECULAR CELL, 2004, 14 (05) :637-646
[79]   Polycomb Group Targeting through Different Binding Partners of RING1B C-Terminal Domain [J].
Wang, Renjing ;
Taylor, Alexander B. ;
Leal, Belinda Z. ;
Chadwell, Linda V. ;
Ilangovan, Udayar ;
Robinson, Angela K. ;
Schirf, Virgil ;
Hart, P. John ;
Lafer, Eileen M. ;
Demeler, Borries ;
Hinck, Andrew P. ;
McEwen, Donald G. ;
Kim, Chongwoo A. .
STRUCTURE, 2010, 18 (08) :966-975
[80]   A Region of the Human HOXD Cluster that Confers Polycomb-Group Responsiveness [J].
Woo, Caroline J. ;
Kharchenko, Peter V. ;
Daheron, Laurence ;
Park, Peter J. ;
Kingston, Robert E. .
CELL, 2010, 140 (01) :99-110