title: Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness.
abstract: In most metazoan nuclei, heterochromatin is located at the nuclear periphery in contact with the nuclear lamina, which provides mechanical stability to the nucleus. We show that in cultured cells, chromatin decompaction by the nucleosome binding protein HMGN5 decreases the sturdiness, elasticity and rigidity of the nucleus. Mice overexpressing HMGN5, either globally or only in the heart, are normal at birth but develop hypertrophic heart with large cardiomyoctyes, deformed nuclei and disrupted lamina and die of cardiac malfunction. Chromatin decompaction is seen in cardiomyocytes of newborn mice but misshaped nuclei with disrupted lamina are seen only in adult cardiomyocytes, suggesting that loss of heterochromatin diminishes the ability of the nucleus to withstand the mechanical forces of the contracting heart. Thus, heterochromatin enhances the ability of the nuclear lamina to maintain the sturdiness and shape of the eukaryotic nucleus; a structural role for chromatin that is distinct from its genetic functions.
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Furusawa
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Rochman
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock 18057, Germany.
authors.forename: Leila
authors.initials: L
authors.lastname: Taher
authors.affiliation: Biomedical Engineering and Physical Science Shared Resource Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Emilios K
authors.initials: EK
authors.lastname: Dimitriadis
authors.affiliation: Electron microscopy laboratory, Leidos Biomedical Research Inc., SAIC-Frederick Inc.,Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.affiliation: Animal Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Stasia
authors.initials: S
authors.lastname: Anderson
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001696:Biomechanical Phenomena; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D048429:Cell Size; D004548:Elasticity; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D024001:HMGN Proteins / Q000235:genetics* / Q000378:metabolism; D006244:Hardness; D006570:Heterochromatin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D006657:Histones / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D041681:NIH 3T3 Cells; D034881:Nuclear Lamina / Q000378:metabolism / Q000648:ultrastructure; D061251:Primary Cell Culture
chemical_list: D024001:HMGN Proteins; D006570:Heterochromatin; D006657:Histones; C498963:Hmgn5 protein, mouse; D034921:Lamin Type B; C045073:Cre recombinase; D019426:Integrases