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

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

• Publication year

  2012

• Venue

  eLife

• Publication date

  2012-12-18

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.7554/eLife.00205PMID 23256043PMCID 3524939
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2012influential reference
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  2012cited by this paper
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  2012influential reference
• An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment

  2011influential reference
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  2011cited by this paper
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  2011cited by this paper
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  2010cited by this paper
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  2010influential reference
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010influential reference
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  2010cited by this paper
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  2010influential reference
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  2010influential reference
• Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination.

  2010influential reference
• Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells.

  2009influential reference
• ChIP-seq: using high-throughput sequencing to discover protein-DNA interactions.

  2009cited by this paper
• Ultrafast and memory-efficient alignment of short DNA sequences to the human genome

  2009influential reference
• CpG islands – ‘A rough guide’

  2009cited by this paper
• The transcriptional repressor RYBP is a natively unfolded protein which folds upon binding to DNA.

  2009cited by this paper
• Mechanisms of Polycomb gene silencing: knowns and unknowns

  2009influential reference
• Secondary DNA structure formation for Hoxb9 promoter and identification of its specific binding protein

  2008cited by this paper
• Model-based Analysis of ChIP-Seq (MACS)

  2008influential reference
• Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains

  2008cited by this paper
• Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity

  2008cited by this paper
• Chromatin modifications and their function.

  2007cited by this paper
• Genome-wide maps of chromatin state in pluripotent and lineage-committed cells

  2007influential reference
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  2007influential reference
• JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes

  2007cited by this paper
• Genome regulation by polycomb and trithorax proteins.

  2007cited by this paper
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  2007cited by this paper
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  2007cited by this paper
• Polycomb/Trithorax response elements and epigenetic memory of cell identity

  2007cited by this paper
• The Polycomb‐associated protein Rybp is a ubiquitin binding protein

  2006cited by this paper
• The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity.

  2006cited by this paper
• Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing

  2006influential reference
• Polycomb complexes repress developmental regulators in murine embryonic stem cells

  2006influential reference
• Faculty Opinions recommendation of Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1b.

  2006cited by this paper
• Genomic DNA methylation: the mark and its mediators.

  2006cited by this paper
• Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions.

  2006influential reference
• Polycomb Group and SCF Ubiquitin Ligases Are Found in a Novel BCOR Complex That Is Recruited to BCL6 Targets

  2006cited by this paper
• Structure of a Bmi-1-Ring1B Polycomb Group Ubiquitin Ligase Complex*

  2006cited by this paper
• Control of developmental regulators by Polycomb in human embryonic stem cells.

  2006influential reference
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  2006cited by this paper
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  2004influential reference
• Propagation of silencing; recruitment and repression of naive chromatin in trans by polycomb repressed chromatin.

  2004cited by this paper
• Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation.

  2004cited by this paper
• Chromatin Compaction by a Polycomb Group Protein Complex

  2004influential reference
• Hierarchical recruitment of polycomb group silencing complexes.

  2004influential reference
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  2004influential reference
• Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments

  2004influential reference
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• DNA methylation patterns and epigenetic memory.

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  1995influential reference
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  1995cited by this paper
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  year unknowncited by this paper
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