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

Anca M Farcas; Neil P Blackledge; Ian Sudbery; Hannah K Long; Joanna F McGouran; Nathan R Rose; Sheena Lee; David Sims; Andrea Cerase; Thomas W Sheahan; Haruhiko Koseki; Neil Brockdorff; Chris P Ponting; Benedikt M Kessler; Robert J Klose

doi:10.7554/eLife.00205

eLife (Dec 2012)

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

Anca M Farcas,
Neil P Blackledge,
Ian Sudbery,
Hannah K Long,
Joanna F McGouran,
Nathan R Rose,
Sheena Lee,
David Sims,
Andrea Cerase,
Thomas W Sheahan,
Haruhiko Koseki,
Neil Brockdorff,
Chris P Ponting,
Benedikt M Kessler,
Robert J Klose

Affiliations

Anca M Farcas: Department of Biochemistry, University of Oxford, Oxford, UK
Neil P Blackledge: Department of Biochemistry, University of Oxford, Oxford, UK
Ian Sudbery: CGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, UK
Hannah K Long: Department of Biochemistry, University of Oxford, Oxford, UK; Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
Joanna F McGouran: Ubiquitin Proteolysis Group, Central Proteomics Facility, Nuffield Department of Clinical Medicine, Centre for Cellular and Molecular Physiology, University of Oxford, UK
Nathan R Rose: Department of Biochemistry, University of Oxford, Oxford, UK
Sheena Lee: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
David Sims: CGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, UK
Andrea Cerase: Department of Biochemistry, University of Oxford, Oxford, UK
Thomas W Sheahan: Department of Biochemistry, University of Oxford, Oxford, UK
Haruhiko Koseki: Laboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan
Neil Brockdorff: Department of Biochemistry, University of Oxford, Oxford, UK
Chris P Ponting: CGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, UK
Benedikt M Kessler: Ubiquitin Proteolysis Group, Central Proteomics Facility, Nuffield Department of Clinical Medicine, Centre for Cellular and Molecular Physiology, University of Oxford, UK
Robert J Klose: Department of Biochemistry, University of Oxford, Oxford, UK

DOI: https://doi.org/10.7554/eLife.00205
Journal volume & issue: Vol. 1

Abstract

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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.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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