title: RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes.
abstract: Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems function to achieve transcriptional regulation remains very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1 (PRC1) is defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication between PRC1 and Polycomb repressive complex 2 (PRC2) which is required for normal histone H3 lysine 27 trimethylation (H3K27me3). Without normal histone modification-dependent communication between PRC1 and PRC2, repressive Polycomb chromatin domains can erode, rendering target genes susceptible to inappropriate gene expression signals. This suggests that activity-based communication and histone modification-dependent thresholds create a localized form of epigenetic memory required for normal PcG chromatin domain function in gene regulation.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Rose
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Hamish W
authors.initials: HW
authors.lastname: King
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Blackledge
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Nadezda A
authors.initials: NA
authors.lastname: Fursova
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Katherine Ji
authors.initials: KJ
authors.lastname: Ember
authors.affiliation: TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Roman
authors.identifier: 0000-0002-9715-5951
authors.initials: R
authors.lastname: Fischer
authors.affiliation: TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United Kingdom.|Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.|Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Robert J
authors.identifier: 0000-0002-8726-7888
authors.initials: RJ
authors.lastname: Klose
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D063185:Epigenetic Repression; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology*; D009124:Muscle Proteins; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D009124:Muscle Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C120616:Rybp protein, mouse; C484486:Yaf2 protein, mouse; D063150:Polycomb Repressive Complex 1
keywords: E3 ubiquitin ligase; Polycomb repressive complex; chromatin; chromosomes; gene expression; genes; histone modification; mouse