title: The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing.
abstract: G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, 35 rue Hélène Brion, 75013 Paris, France. Electronic address: chiara.mozzetta@univ-paris-diderot.fr.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mozzetta
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pontis
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Fritsch
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robin
authors.affiliation: Institut Curie, 26 rue d'Ulm, 75005 Paris, France; UMR3215 CNRS, 26 rue d'Ulm, 75005 Paris, France; U934 INSERM, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Manuela
authors.initials: M
authors.lastname: Portoso
authors.affiliation: Institut Pasteur, PF2 Plate-forme Transcriptome et Epigénome, 28 rue du Dr Roux, Paris, 75015 France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Proux
authors.affiliation: Institut Curie, 26 rue d'Ulm, 75005 Paris, France; UMR3215 CNRS, 26 rue d'Ulm, 75005 Paris, France; U934 INSERM, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Margueron
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, 35 rue Hélène Brion, 75013 Paris, France. Electronic address: slimane.aitsiali@univ-paris-diderot.fr.
authors.forename: Slimane
authors.initials: S
authors.lastname: Ait-Si-Ali
mesh_terms: D000071221:Enhancer of Zeste Homolog 2 Protein; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006367:HeLa Cells; D006649:Histocompatibility Antigens / Q000378:metabolism / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D063151:Polycomb Repressive Complex 2 / Q000502:physiology*; D011401:Promoter Regions, Genetic
chemical_list: D006649:Histocompatibility Antigens; D006657:Histones; C455847:EHMT1 protein, human; C445405:EHMT2 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2