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...
Main Authors: | , , , , , , , , , , , , , , |
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Format: | Journal article |
Language: | English |
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eLife Sciences Publications
2012
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_version_ | 1797089679427764224 |
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author | Farcas, A Blackledge, N Sudbery, I Long, H McGouran, J Rose, N Lee, S Sims, D Cerase, A Sheahan, T Koseki, H Brockdorff, N Ponting, C Kessler, B Klose, R |
author_facet | Farcas, A Blackledge, N Sudbery, I Long, H McGouran, J Rose, N Lee, S Sims, D Cerase, A Sheahan, T Koseki, H Brockdorff, N Ponting, C Kessler, B Klose, R |
author_sort | Farcas, A |
collection | OXFORD |
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. |
first_indexed | 2024-03-07T03:07:31Z |
format | Journal article |
id | oxford-uuid:b30fa840-bc68-484d-9607-7007359303f5 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T03:07:31Z |
publishDate | 2012 |
publisher | eLife Sciences Publications |
record_format | dspace |
spelling | oxford-uuid:b30fa840-bc68-484d-9607-7007359303f52022-03-27T04:16:17ZKDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islandsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b30fa840-bc68-484d-9607-7007359303f5EnglishSymplectic Elements at OxfordeLife Sciences Publications2012Farcas, ABlackledge, NSudbery, ILong, HMcGouran, JRose, NLee, SSims, DCerase, ASheahan, TKoseki, HBrockdorff, NPonting, CKessler, BKlose, RCpG 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. |
spellingShingle | Farcas, A Blackledge, N Sudbery, I Long, H McGouran, J Rose, N Lee, S Sims, D Cerase, A Sheahan, T Koseki, H Brockdorff, N Ponting, C Kessler, B Klose, R KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands |
title | 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_short | 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 |
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