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...

Full description

Bibliographic Details
Main Authors: 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
Format: Journal article
Language:English
Published: eLife Sciences Publications 2012
_version_ 1797089679427764224
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
work_keys_str_mv AT farcasa kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT blackledgen kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT sudberyi kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT longh kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT mcgouranj kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT rosen kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT lees kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT simsd kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT cerasea kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT sheahant kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT kosekih kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT brockdorffn kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT pontingc kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT kesslerb kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands
AT kloser kdm2blinksthepolycombrepressivecomplex1prc1torecognitionofcpgislands