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XB-ART-47172
Elife. December 18, 2012; 1 e00205.

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

Farcas AM , Blackledge NP , Sudbery I , Long HK , McGouran JF , Rose NR , Lee S , Sims D , Cerase A , Sheahan TW , Koseki H , Brockdorff N , Ponting CP , Kessler BM , Klose RJ .


Abstract
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.

PubMed ID: 23256043
PMC ID: PMC3524939
Article link: Elife.
Grant support: 081385 Wellcome Trust , 090532/Z/09/Z Wellcome Trust , 081385 Wellcome Trust , 103768 Wellcome Trust , MC_U137761446 Medical Research Council , 090532/Z/09/Z Wellcome Trust , MRC_MC_U137761446 Medical Research Council , WT081385 Wellcome Trust , WT103768 Wellcome Trust , 090532/Z/09/Z Wellcome Trust , 081385 Wellcome Trust , 103768 Wellcome Trust , MC_U137761446 Medical Research Council , 090532/Z/09/Z Wellcome Trust

Genes referenced: act3 adss atf3 bcor bcorl1 eed ezh2 gapdh hist2h2ab kdm2a kdm2b lhx4 lmna pcgf1 prc1 rnf2 rybp skp1 tbx2 yaf2


References:
Arrigoni, 2006, Pubmed[+]


Article Images: [+] show captions

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