title: KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands.
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.
authors.affiliation: Department of Biochemistry ,  University of Oxford ,  Oxford ,  UK.
authors.forename: Anca M
authors.initials: AM
authors.lastname: Farcas
authors.forename: Neil P
authors.initials: NP
authors.lastname: Blackledge
authors.forename: Ian
authors.initials: I
authors.lastname: Sudbery
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Long
authors.forename: Joanna F
authors.initials: JF
authors.lastname: McGouran
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Rose
authors.forename: Sheena
authors.initials: S
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Sims
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerase
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Sheahan
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Neil
authors.initials: N
authors.lastname: Brockdorff
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Klose
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D016678:Genome; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D063146:Polycomb-Group Proteins / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D044783:F-Box Proteins; D006657:Histones; D063146:Polycomb-Group Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C534524:KDM2A protein, human