XB-ART-47172
Elife
December 18, 2012;
1
e00205.
KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands.
Farcas AM
,
Blackledge NP
,
Sudbery I
,
Long HK
,
McGouran JF
,
Rose NR
,
Lee S
,
Sims D
,
Cerase A
,
Sheahan TW
,
Koseki H
,
Brockdorff N
,
Ponting CP
,
Kessler BM
,
Klose RJ
.
Abstract
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.DOI:http://dx.doi.org/10.7554/eLife.00205.001.
PubMed ID: 23256043
PMC ID: PMC3524939
Article link: Elife
Grant support: [+]
081385 Wellcome Trust , 090532/Z/09/Z Wellcome Trust , 103768 Wellcome Trust , MC_U137761446 Medical Research Council , MRC_MC_U137761446 Medical Research Council , WT081385 Wellcome Trust , WT103768 Wellcome Trust , MC_EX_G1000902 Medical Research Council
Species referenced: Xenopus
Genes referenced: acta4 adss2 atf3 bcor bcorl1 eed ezh2 h2ac21 kdm2a kdm2b lhx4 lmna pcgf1 prc1 rnf2 rybp skp1 tbx2 yaf2
Article Images: [+] show captions
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Wang, Hierarchical recruitment of polycomb group silencing complexes. 2004, Pubmed
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Wang, Role of histone H2A ubiquitination in Polycomb silencing. 2004, Pubmed
Woo, A region of the human HOXD cluster that confers polycomb-group responsiveness. 2010, Pubmed
Yamagishi, Secondary DNA structure formation for Hoxb9 promoter and identification of its specific binding protein. 2008, Pubmed
Yu, Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. 2012, Pubmed
Yuan, Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. 2012, Pubmed
Zhang, Model-based analysis of ChIP-Seq (MACS). 2008, Pubmed
Zhou, Recognition of CpG island chromatin by KDM2A requires direct and specific interaction with linker DNA. 2011, Pubmed , Xenbase
de Napoles, Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. 2004, Pubmed
Atsuta, Production of monoclonal antibodies against mammalian Ring1B proteins. 2001, Pubmed
Ben-Saadon, The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity. 2006, Pubmed
Bird, DNA methylation patterns and epigenetic memory. 2002, Pubmed
Blackledge, Bio-CAP: a versatile and highly sensitive technique to purify and characterise regions of non-methylated DNA. 2012, Pubmed
Blackledge, CpG island chromatin: a platform for gene regulation. 2011, Pubmed
Blackledge, CpG islands recruit a histone H3 lysine 36 demethylase. 2010, Pubmed
Boyer, Polycomb complexes repress developmental regulators in murine embryonic stem cells. 2006, Pubmed
Bracken, Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. 2006, Pubmed
Buchwald, Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1b. 2006, Pubmed
Butler, Histone-modifying enzymes: regulators of developmental decisions and drivers of human disease. 2012, Pubmed
Cao, Role of histone H3 lysine 27 methylation in Polycomb-group silencing. 2002, Pubmed
Cao, Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. 2005, Pubmed
Carrozza, Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. 2005, Pubmed
Carvalho, A framework for oligonucleotide microarray preprocessing. 2010, Pubmed
Czermin, Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. 2002, Pubmed
Deaton, CpG islands and the regulation of transcription. 2011, Pubmed
Dietrich, REST-mediated recruitment of polycomb repressor complexes in mammalian cells. 2012, Pubmed
Endoh, Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity. 2008, Pubmed
Endoh, Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity. 2012, Pubmed
Eskeland, Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. 2010, Pubmed
Fischer, Discovery of candidate serum proteomic and metabolomic biomarkers in ankylosing spondylitis. 2012, Pubmed
Francis, Chromatin compaction by a polycomb group protein complex. 2004, Pubmed
Frescas, JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes. 2007, Pubmed
Gao, PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. 2012, Pubmed
Gearhart, Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets. 2006, Pubmed
Greer, Histone methylation: a dynamic mark in health, disease and inheritance. 2012, Pubmed
Hisada, RYBP represses endogenous retroviruses and preimplantation- and germ line-specific genes in mouse embryonic stem cells. 2012, Pubmed
Illingworth, Orphan CpG islands identify numerous conserved promoters in the mammalian genome. 2010, Pubmed
Illingworth, CpG islands--'a rough guide'. 2009, Pubmed
Illingworth, PRC1 and PRC2 are not required for targeting of H2A.Z to developmental genes in embryonic stem cells. 2012, Pubmed
Kanhere, Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. 2010, Pubmed
Kim, AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2. 2009, Pubmed
Klose, MeCP2 behaves as an elongated monomer that does not stably associate with the Sin3a chromatin remodeling complex. 2004, Pubmed , Xenbase
Klose, Genomic DNA methylation: the mark and its mediators. 2006, Pubmed
Klymenko, The histone methyltransferases Trithorax and Ash1 prevent transcriptional silencing by Polycomb group proteins. 2004, Pubmed
Kouzarides, Chromatin modifications and their function. 2007, Pubmed
Koyama-Nasu, The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun. 2007, Pubmed
Ku, Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. 2008, Pubmed
Kuzmichev, Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. 2002, Pubmed
Langmead, Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. 2009, Pubmed
Lavigne, Propagation of silencing; recruitment and repression of naive chromatin in trans by polycomb repressed chromatin. 2004, Pubmed
Lee, CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1/COMPASS complex. 2005, Pubmed
Lee, Control of developmental regulators by Polycomb in human embryonic stem cells. 2006, Pubmed
Leeb, Polycomb complexes act redundantly to repress genomic repeats and genes. 2010, Pubmed
Leeb, Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells. 2007, Pubmed
Levine, The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans. 2002, Pubmed
Li, Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex. 2006, Pubmed
Li, Jarid2 and PRC2, partners in regulating gene expression. 2010, Pubmed
Lynch, An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment. 2012, Pubmed
Mendenhall, GC-rich sequence elements recruit PRC2 in mammalian ES cells. 2010, Pubmed
Mikkelsen, Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. 2007, Pubmed
Min, Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. 2003, Pubmed
Müller, Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. 2002, Pubmed
Neira, The transcriptional repressor RYBP is a natively unfolded protein which folds upon binding to DNA. 2009, Pubmed
Pasini, The polycomb group protein Suz12 is required for embryonic stem cell differentiation. 2007, Pubmed
Peng, Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. 2010, Pubmed , Xenbase
Peters, Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. 2003, Pubmed
Poux, The Drosophila trithorax protein is a coactivator required to prevent re-establishment of polycomb silencing. 2002, Pubmed
Quinlan, BEDTools: a flexible suite of utilities for comparing genomic features. 2010, Pubmed
Ren, REST interacts with Cbx proteins and regulates polycomb repressive complex 1 occupancy at RE1 elements. 2011, Pubmed
Ringrose, Polycomb/Trithorax response elements and epigenetic memory of cell identity. 2006, Pubmed
Robin, Post-translational modifications of histones H3 and H4 associated with the histone methyltransferases Suv39h1 and G9a. 2008, Pubmed
Schmidt, ChIP-seq: using high-throughput sequencing to discover protein-DNA interactions. 2009, Pubmed
Schoeftner, Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. 2006, Pubmed
Schuettengruber, Genome regulation by polycomb and trithorax proteins. 2007, Pubmed
Shao, Stabilization of chromatin structure by PRC1, a Polycomb complex. 1999, Pubmed
Simon, Mechanisms of polycomb gene silencing: knowns and unknowns. 2009, Pubmed
Smyth, Linear models and empirical bayes methods for assessing differential expression in microarray experiments. 2006, Pubmed
Strahl, Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. 2002, Pubmed
Sánchez, Proteomics analysis of Ring1B/Rnf2 interactors identifies a novel complex with the Fbxl10/Jhdm1B histone demethylase and the Bcl6 interacting corepressor. 2007, Pubmed
Tavares, RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3. 2012, Pubmed
Thomson, CpG islands influence chromatin structure via the CpG-binding protein Cfp1. 2010, Pubmed
Vassilev, The levels of ubiquitinated histone H2A are highly upregulated in transformed human cells: partial colocalization of uH2A clusters and PCNA/cyclin foci in a fraction of cells in S-phase. 1995, Pubmed
Wang, Hierarchical recruitment of polycomb group silencing complexes. 2004, Pubmed
Wang, Polycomb group targeting through different binding partners of RING1B C-terminal domain. 2010, Pubmed
Wang, Role of histone H2A ubiquitination in Polycomb silencing. 2004, Pubmed
Woo, A region of the human HOXD cluster that confers polycomb-group responsiveness. 2010, Pubmed
Yamagishi, Secondary DNA structure formation for Hoxb9 promoter and identification of its specific binding protein. 2008, Pubmed
Yu, Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. 2012, Pubmed
Yuan, Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. 2012, Pubmed
Zhang, Model-based analysis of ChIP-Seq (MACS). 2008, Pubmed
Zhou, Recognition of CpG island chromatin by KDM2A requires direct and specific interaction with linker DNA. 2011, Pubmed , Xenbase
de Napoles, Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. 2004, Pubmed