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 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.
['Farcas|Anca M|AM|', 'Blackledge|Neil P|NP|', 'Sudbery|Ian|I|', 'Long|Hannah K|HK|', 'McGouran|Joanna F|JF|', 'Rose|Nathan R|NR|', 'Lee|Sheena|S|', 'Sims|David|D|', 'Cerase|Andrea|A|', 'Sheahan|Thomas W|TW|', 'Koseki|Haruhiko|H|', 'Brockdorff|Neil|N|', 'Ponting|Chris P|CP|', 'Kessler|Benedikt M|BM|', 'Klose|Robert J|RJ|']
D000818:Animals D045744:Cell Line, Tumor D018899:CpG Islands D019175:DNA Methylation D044783:F-Box Proteins D020868:Gene Silencing D016678:Genome D006657:Histones D006801:Humans D056484:Jumonji Domain-Containing Histone Demethylases D051379:Mice D063146:Polycomb-Group Proteins D054875:Ubiquitination
CpG island Chicken Chromatin Demethylase Epigenetics Human Methylation Mouse Transcription Xenopus Zebrafish