title: The interaction of PRC2 with RNA or chromatin is mutually antagonistic.
abstract: Polycomb repressive complex 2 (PRC2) modifies chromatin to maintain genes in a repressed state during development. PRC2 is primarily associated with CpG islands at repressed genes and also possesses RNA binding activity. However, the RNAs that bind PRC2 in cells, the subunits that mediate these interactions, and the role of RNA in PRC2 recruitment to chromatin all remain unclear. By performing iCLIP for PRC2 in comparison with other RNA binding proteins, we show here that PRC2 binds nascent RNA at essentially all active genes. Although interacting with RNA promiscuously, PRC2 binding is enriched at specific locations within RNAs, primarily exon-intron boundaries and the 3' UTR. Deletion of other PRC2 subunits reveals that SUZ12 is sufficient to establish this RNA binding profile. Contrary to prevailing models, we also demonstrate that the interaction of PRC2 with RNA or chromatin is mutually antagonistic in cells and in vitro. RNA degradation in cells triggers PRC2 recruitment to CpG islands at active genes. Correspondingly, the release of PRC2 from chromatin in cells increases RNA binding. Consistent with this, RNA and nucleosomes compete for PRC2 binding in vitro. We propose that RNA prevents PRC2 recruitment to chromatin at active genes and that mutual antagonism between RNA and chromatin underlies the pattern of PRC2 chromatin association across the genome.
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Manuel
authors.initials: M
authors.lastname: Beltran
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Yates
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Lenka
authors.initials: L
authors.lastname: Skalska
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Marcus
authors.initials: M
authors.lastname: Dawson
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Filipa P
authors.initials: FP
authors.lastname: Reis
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Keijo
authors.initials: K
authors.lastname: Viiri
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Fisher
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom;
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Sibley
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Foster
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
authors.forename: Till
authors.initials: T
authors.lastname: Bartke
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom;
authors.forename: Jernej
authors.identifier: 0000-0002-2452-4277
authors.initials: J
authors.lastname: Ule
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Richard G
authors.identifier: 0000-0002-2946-6811
authors.initials: RG
authors.lastname: Jenner
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D005091:Exons; D005786:Gene Expression Regulation; D007438:Introns; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology; D009707:Nucleosomes / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D002843:Chromatin; D009707:Nucleosomes; D012333:RNA, Messenger; C494163:Suz12 protein, mouse; D063151:Polycomb Repressive Complex 2