title: High mobility group N proteins modulate the fidelity of the cellular transcriptional profile in a tissue- and variant-specific manner.
abstract: The nuclei of most vertebrate cells contain members of the high mobility group N (HMGN) protein family, which bind specifically to nucleosome core particles and affect chromatin structure and function, including transcription. Here, we study the biological role of this protein family by systematic analysis of phenotypes and tissue transcription profiles in mice lacking functional HMGN variants. Phenotypic analysis of Hmgn1(tm1/tm1), Hmgn3(tm1/tm1), and Hmgn5(tm1/tm1) mice and their wild type littermates with a battery of standardized tests uncovered variant-specific abnormalities. Gene expression analysis of four different tissues in each of the Hmgn(tm1/tm1) lines reveals very little overlap between genes affected by specific variants in different tissues. Pathway analysis reveals that loss of an HMGN variant subtly affects expression of numerous genes in specific biological processes. We conclude that within the biological framework of an entire organism, HMGNs modulate the fidelity of the cellular transcriptional profile in a tissue- and HMGN variant-specific manner.
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Kugler
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Horsch
authors.affiliation: Computational Biology Branch, NCBI, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Di
authors.initials: D
authors.lastname: Huang
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Takashi
authors.initials: T
authors.lastname: Furusawa
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Mark
authors.initials: M
authors.lastname: Rochman
authors.affiliation: German Mouse Clinic, Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Lillian
authors.initials: L
authors.lastname: Garrett
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Lore
authors.initials: L
authors.lastname: Becker
authors.affiliation: German Mouse Clinic, Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Lung Research, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bohla
authors.affiliation: German Mouse Clinic, Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Racz
authors.affiliation: Center of Allergy and Environment, Technische Universität München, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Dermatology and Allergy, Biederstein, Technische Universität München and Clinical Research Division of Molecular and Clinical Allergotoxicology, Technische Universität München, Munich, Germany.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Aguilar-Pimentel
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Institute of Medical Microbiology, Immunology, and Hygiene, Technische Universität München, München, Germany.
authors.forename: Thure
authors.initials: T
authors.lastname: Adler
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85350 Freising-Weihenstephan, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.affiliation: Institute of Medical Microbiology, Immunology, and Hygiene, Technische Universität München, München, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: German Mouse Clinic, Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Lung Research, Munich, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, Munich, Germany; German Center for Vertigo and Balance Disorders, Technische Universität München, Munich, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen-German Center for Neurodegenerative Diseases, Site Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.affiliation: Department of Dermatology and Allergy, Biederstein, Technische Universität München and Clinical Research Division of Molecular and Clinical Allergotoxicology, Technische Universität München, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ollert
authors.affiliation: German Mouse Clinic, Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Lung Research, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Stöger
authors.affiliation: Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.affiliation: German Mouse Clinic, Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen-German Center for Neurodegenerative Diseases, Site Munich, Munich, Germany; Max Planck Institute of Psychiatry, Munich, Germany; Developmental Genetics, Technische Universität München c/o Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.affiliation: German Mouse Clinic, Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Lung Research, Munich, Germany.
authors.forename: Ali Önder
authors.initials: AÖ
authors.lastname: Yildirim
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising-Weihenstephan, Germany; German Center for Vertigo and Balance Disorders, Technische Universität München, Munich, Germany; German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Benny
authors.initials: B
authors.lastname: Garfinkel
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Orly
authors.affiliation: Computational Biology Branch, NCBI, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ovcharenko
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892. Electronic address: bustin@helix.nih.gov.
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D024001:HMGN Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009928:Organ Specificity / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D024001:HMGN Proteins
keywords: Chromatin; Chromosomes/Non-histone Chromosomal Proteins; Gene Regulation; HMG Proteins; Mouse Physiology; Transcriptomics; Transgenic Mice