title: Unexpected Distinct Roles of the Related Histone H3 Lysine 9 Methyltransferases G9a and G9a-Like Protein in Myoblasts.
abstract: Lysine methyltransferases G9a and GLP (G9a-like protein) are highly homologous and form functional heterodimeric complexes that establish mono- and dimethylation on histone H3 lysine 9 (H3K9me1, H3K9me2) in euchromatin. Here, we describe unexpected distinct roles for G9a and GLP in skeletal muscle terminal differentiation. Indeed, gain- or loss-of-function assays in myoblasts showed, in agreement with previous reports, that G9a inhibits terminal differentiation. While GLP plays a more intricate role in muscle differentiation,in one hand, both GLP gain and loss of function inhibit late steps of differentiation; on the other hand, in contrast to G9a, GLP overexpression promotes abnormal precocious expression of muscle differentiation-specific genes already in proliferating myoblasts. In agreement, transcriptomic analysis indicates that G9a and GLP regulate different sets of genes. Thus, GLP, but not G9a, inhibits proteasome subunit-encoding genes expression, resulting in an inhibition of the proteasome activities. Subsequently, GLP, but not G9a, overexpression stabilizes MyoD that is likely to be responsible for muscle markers expression in proliferating myoblasts.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Valentine
authors.initials: V
authors.lastname: Battisti
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pontis
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Boyarchuk
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Fritsch
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, 35 rue Hélène Brion, 75013 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robin
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, 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
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, 35 rue Hélène Brion, 75013 Paris, France. Electronic address: veronique.joliot@univ-paris-diderot.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Joliot
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D024510:Muscle Development / Q000502:physiology; D032446:Myoblasts / Q000378:metabolism*
chemical_list: D006657:Histones; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine
keywords: EHMT; differentiation; histone methylation; muscle; proliferation