title: RYBP and Cbx7 define specific biological functions of polycomb complexes in mouse embryonic stem cells.
abstract: The Polycomb repressive complex 1 (PRC1) is required for decisions of stem cell fate. In mouse embryonic stem cells (ESCs), two major variations of PRC1 complex, defined by the mutually exclusive presence of Cbx7 or RYBP, have been identified. Here, we show that although the genomic localization of the Cbx7- and RYBP-containing PRC1 complexes overlaps in certain genes, it can also be mutually exclusive. At the molecular level, Cbx7 is necessary for recruitment of Ring1B to chromatin, whereas RYBP enhances the PRC1 enzymatic activity. Genes occupied by RYBP show lower levels of Ring1B and H2AK119ub and are consequently more highly transcribed than those bound by Cbx7. At the functional level, we show that genes occupied by RYBP are primarily involved in the regulation of metabolism and cell-cycle progression, whereas those bound by Cbx7 predominantly control early-lineage commitment of ESCs. Altogether, our results indicate that different PRC1 subtypes establish a complex pattern of gene regulation that regulates common and nonoverlapping aspects of ESC pluripotency and differentiation.
authors.affiliation: Centre for Genomic Regulation and UPF, Dr. Aiguader 88, 08003 Barcelona, Spain. lluis.morey@crg.eu
authors.forename: Lluis
authors.initials: L
authors.lastname: Morey
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloia
authors.forename: Luca
authors.initials: L
authors.lastname: Cozzuto
authors.forename: Salvador Aznar
authors.initials: SA
authors.lastname: Benitah
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D016678:Genome / Q000235:genetics; D006801:Humans; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C519505:Cbx7 protein, mouse; D002843:Chromatin; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C120616:Rybp protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases