title: Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation.
abstract: Polycomb repressive complex 1 (PRC1) catalyzes lysine 119 monoubiquitylation on H2A (H2AK119ub1) and regulates pluripotency in embryonic stem cells (ESCs). However, the mechanisms controlling the binding of PRC1 to genomic sites and its catalytic activity are poorly understood. Here, we show that Fbxl10 interacts with Ring1B and Nspc1, forming a noncanonical PRC1 that is required for H2AK119ub1 in mouse ESCs. Genome-wide analyses reveal that Fbxl10 preferentially binds to CpG islands and colocalizes with Ring1B on Polycomb target genes. Notably, Fbxl10 depletion causes a decrease in Ring1B binding to target genes and a major loss of H2AK119ub1. Furthermore, genetic analyses demonstrate that Fbxl10 DNA binding capability and integration into PRC1 are required for H2AK119 ubiquitylation. ESCs lacking Fbxl10, like previously characterized Polycomb mutants, cannot differentiate properly. These results demonstrate that Fbxl10 has a key role in regulating Ring1B recruitment to its target genes and H2AK119 ubiquitylation in ESCs.
authors: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors: Xudong
authors: X
authors: Wu
authors: Jens Vilstrup
authors: JV
authors: Johansen
authors: Kristian
authors: K
authors: Helin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D018899:CpG Islands; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000502:physiology; D044127:Epigenesis, Genetic; D044783:F-Box Proteins / Q000502:physiology*; D016678:Genome; D006657:Histones / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D044783:F-Box Proteins; D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; C524747:Kdm2b protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases