title: MacroH2A histone variants maintain nuclear organization and heterochromatin architecture.
abstract: Genetic loss-of-function studies on development, cancer and somatic cell reprogramming have suggested that the group of macroH2A histone variants might function through stabilizing the differentiated state by a yet unknown mechanism. Here, we present results demonstrating that macroH2A variants have a major function in maintaining nuclear organization and heterochromatin architecture. Specifically, we find that a substantial amount of macroH2A is associated with heterochromatic repeat sequences. We further identify macroH2A on sites of interstitial heterochromatin decorated by histone H3 trimethylated on K9 (H3K9me3). Loss of macroH2A leads to major defects in nuclear organization, including reduced nuclear circularity, disruption of nucleoli and a global loss of dense heterochromatin. Domains formed by DNA repeat sequences are disorganized, expanded and fragmented, and mildly re-expressed when depleted of macroH2A. At the molecular level, we find that macroH2A is required for the interaction of repeat sequences with the nucleostructural protein lamin B1. Taken together, our results argue that a major function of macroH2A histone variants is to link nucleosome composition to higher-order chromatin architecture.
authors.affiliation: Josep Carreras Leukaemia Research Institute (IJC), Campus ICO - Germans Trias i Pujol, Campus Can Ruti, Badalona 08916, Spain.|Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, Badalona 08916, Spain.
authors.forename: Julien
authors.initials: J
authors.lastname: Douet
authors.affiliation: Josep Carreras Leukaemia Research Institute (IJC), Campus ICO - Germans Trias i Pujol, Campus Can Ruti, Badalona 08916, Spain.|Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, Badalona 08916, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Corujo
authors.affiliation: Josep Carreras Leukaemia Research Institute (IJC), Campus ICO - Germans Trias i Pujol, Campus Can Ruti, Badalona 08916, Spain.|Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, Badalona 08916, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Malinverni
authors.affiliation: Cell and tissue biology unit, GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Justine
authors.initials: J
authors.lastname: Renauld
authors.affiliation: BioMedical Center and Center for Integrated Protein Sciences Munich, Ludwig-Maximilians-University of Munich, Großhaderner Straße 9, Planegg-Martinsried 82152, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Sansoni
authors.affiliation: Josep Carreras Leukaemia Research Institute (IJC), Campus ICO - Germans Trias i Pujol, Campus Can Ruti, Badalona 08916, Spain.
authors.forename: Melanija
authors.initials: M
authors.lastname: Posavec Marjanović
authors.affiliation: Josep Carreras Leukaemia Research Institute (IJC), Campus ICO - Germans Trias i Pujol, Campus Can Ruti, Badalona 08916, Spain.
authors.forename: Neus
authors.identifier: 0000-0002-9548-3927
authors.initials: N
authors.lastname: Cantariño
authors.affiliation: Josep Carreras Leukaemia Research Institute (IJC), Campus ICO - Germans Trias i Pujol, Campus Can Ruti, Badalona 08916, Spain.|Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, Badalona 08916, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Valero
authors.affiliation: Université de Lyon, Ecole normale Supérieure de Lyon, Centre de Recherche en Cancérologie de Lyon, Cancer Cell Plasticity Department, UMR INSERM 1052 CNRS5286, Centre Léon Bérard, 69008 Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Mongelard
authors.affiliation: Université de Lyon, Ecole normale Supérieure de Lyon, Centre de Recherche en Cancérologie de Lyon, Cancer Cell Plasticity Department, UMR INSERM 1052 CNRS5286, Centre Léon Bérard, 69008 Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouvet
authors.affiliation: BioMedical Center and Center for Integrated Protein Sciences Munich, Ludwig-Maximilians-University of Munich, Großhaderner Straße 9, Planegg-Martinsried 82152, Germany.
authors.forename: Axel
authors.identifier: 0000-0003-2993-8249
authors.initials: A
authors.lastname: Imhof
authors.affiliation: Cell and tissue biology unit, GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Thiry
authors.affiliation: Josep Carreras Leukaemia Research Institute (IJC), Campus ICO - Germans Trias i Pujol, Campus Can Ruti, Badalona 08916, Spain mbuschbeck@carrerasresearch.org.|Program of Predictive and Personalized Medicine of Cancer, Germans Trias and Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, Badalona 08916, Spain.
authors.forename: Marcus
authors.identifier: 0000-0002-3218-4567
authors.initials: M
authors.lastname: Buschbeck
mesh_terms: D002466:Cell Nucleolus / Q000378:metabolism / Q000648:ultrastructure; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006570:Heterochromatin / Q000378:metabolism* / Q000648:ultrastructure; D006657:Histones / Q000378:metabolism*; D006801:Humans; D034921:Lamin Type B / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D011485:Protein Binding
chemical_list: D006570:Heterochromatin; D006657:Histones; D034921:Lamin Type B; C120756:macroH2A histone; D008239:Lysine
keywords: DNA repeats; Heterochromatin; Histone variant; Nuclear organization