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 fo...
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eLife Sciences Publications Ltd
2012-12-01
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| Online Access: | https://elifesciences.org/articles/00205 |
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doaj-1833a1a5ee634de494ff1570787fe8ab2021-04-30T23:25:48ZengeLife Sciences Publications LtdeLife2050-084X2012-12-01110.7554/eLife.00205KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islandsAnca M Farcas0Neil P Blackledge1Ian Sudbery2Hannah K Long3Joanna F McGouran4Nathan R Rose5Sheena Lee6David Sims7Andrea Cerase8Thomas W Sheahan9Haruhiko Koseki10Neil Brockdorff11Chris P Ponting12Benedikt M Kessler13Robert J Klose14Department of Biochemistry, University of Oxford, Oxford, UKDepartment of Biochemistry, University of Oxford, Oxford, UKCGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, UKDepartment of Biochemistry, University of Oxford, Oxford, UK; Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UKUbiquitin Proteolysis Group, Central Proteomics Facility, Nuffield Department of Clinical Medicine, Centre for Cellular and Molecular Physiology, University of Oxford, UKDepartment of Biochemistry, University of Oxford, Oxford, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UKCGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, UKDepartment of Biochemistry, University of Oxford, Oxford, UKDepartment of Biochemistry, University of Oxford, Oxford, UKLaboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology, Yokohama, JapanDepartment of Biochemistry, University of Oxford, Oxford, UKCGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, UKUbiquitin Proteolysis Group, Central Proteomics Facility, Nuffield Department of Clinical Medicine, Centre for Cellular and Molecular Physiology, University of Oxford, UKDepartment of Biochemistry, University of Oxford, Oxford, UKCpG 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.https://elifesciences.org/articles/00205CpG islandChromatinepigeneticTranscriptionMethylationDemethylase |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands eLife CpG island Chromatin epigenetic Transcription Methylation Demethylase |
| author_facet |
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 |
| author_sort |
Anca M Farcas |
| title |
KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands |
| title_short |
KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands |
| title_full |
KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands |
| title_fullStr |
KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands |
| title_full_unstemmed |
KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands |
| title_sort |
kdm2b links the polycomb repressive complex 1 (prc1) to recognition of cpg islands |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2012-12-01 |
| description |
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. |
| topic |
CpG island Chromatin epigenetic Transcription Methylation Demethylase |
| url |
https://elifesciences.org/articles/00205 |
| work_keys_str_mv |
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