title: Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation.
abstract: Polycomb Group (PcG) proteins maintain transcriptional repression throughout development, mostly by regulating chromatin structure. Polycomb Repressive Complex 2 (PRC2), a component of the Polycomb machinery, is responsible for the methylation of histone H3 lysine 27 (H3K27me2/3). Jarid2 was previously identified as a cofactor of PRC2, regulating PRC2 targeting to chromatin and its enzymatic activity. Deletion of Jarid2 leads to impaired orchestration of gene expression during cell lineage commitment. Here, we reveal an unexpected crosstalk between Jarid2 and PRC2, with Jarid2 being methylated by PRC2. This modification is recognized by the Eed core component of PRC2 and triggers an allosteric activation of PRC2's enzymatic activity. We show that Jarid2 methylation is important to promote PRC2 activity at a locus devoid of H3K27me3 and for the correct deposition of this mark during cell differentiation. Our results uncover a regulation loop where Jarid2 methylation fine-tunes PRC2 activity depending on the chromatin context.
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Serena
authors.initials: S
authors.lastname: Sanulli
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, London, Mill Hill NW7 1AA, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Justin
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U900, 26 Rue d'Ulm, 75005 Paris, France; Mines ParisTech, 35 Rue Saint Honoré, 77305 Fontainebleau, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Teissandier
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Ancelin
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Manuela
authors.initials: M
authors.lastname: Portoso
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Caron
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Michaud
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; Laboratory of Proteomics and Mass Spectrometry, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Berangère
authors.initials: B
authors.lastname: Lombard
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Simao T
authors.initials: ST
authors.lastname: da Rocha
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, London, Mill Hill NW7 1AA, UK.
authors.forename: John
authors.initials: J
authors.lastname: Offer
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; Laboratory of Proteomics and Mass Spectrometry, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U900, 26 Rue d'Ulm, 75005 Paris, France; Mines ParisTech, 35 Rue Saint Honoré, 77305 Fontainebleau, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Wassef
authors.affiliation: Sorbonnes Universités, UPMC Univ Paris 06, CNRS, ENS, UMR7203 LBM, 4 Place Jussieu, 75005 Paris, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burlina
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, London, Mill Hill NW7 1AA, UK.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Gamblin
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France. Electronic address: raphael.margueron@curie.fr.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Margueron
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D057809:HEK293 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D018345:Mice, Knockout; D008957:Models, Genetic; D009154:Mutation; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; C547777:JARID2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D008239:Lysine