title: Atrx promotes heterochromatin formation at retrotransposons.
abstract: More than 50% of mammalian genomes consist of retrotransposon sequences. Silencing of retrotransposons by heterochromatin is essential to ensure genomic stability and transcriptional integrity. Here, we identified a short sequence element in intracisternal A particle (IAP) retrotransposons that is sufficient to trigger heterochromatin formation. We used this sequence in a genome-wide shRNA screen and identified the chromatin remodeler Atrx as a novel regulator of IAP silencing. Atrx binds to IAP elements and is necessary for efficient heterochromatin formation. In addition, Atrx facilitates a robust and largely inaccessible heterochromatin structure as Atrx knockout cells display increased chromatin accessibility at retrotransposons and non-repetitive heterochromatic loci. In summary, we demonstrate a direct role of Atrx in the establishment and robust maintenance of heterochromatin.
authors.affiliation: Adolf-Butenandt-Institute, Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPS), Munich, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Sadic
authors.affiliation: Adolf-Butenandt-Institute, Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPS), Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmidt
authors.affiliation: Adolf-Butenandt-Institute, Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPS), Munich, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Groh
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany Center for Mathematics, Chair of Mathematical Modeling of Biological Systems, Technische Universität München, Garching, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kondofersky
authors.affiliation: Helmholtz Zentrum München, Institute of Molecular Immunology, Munich, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Ellwart
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany Center for Mathematics, Chair of Mathematical Modeling of Biological Systems, Technische Universität München, Garching, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Fuchs
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany Center for Mathematics, Chair of Mathematical Modeling of Biological Systems, Technische Universität München, Garching, Germany.
authors.forename: Fabian J
authors.initials: FJ
authors.lastname: Theis
authors.affiliation: Adolf-Butenandt-Institute, Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPS), Munich, Germany gunnar.schotta@med.uni-muenchen.de.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schotta
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D007426:Genes, Intracisternal A-Particle; D042822:Genomic Instability; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D000075924:X-linked Nuclear Protein
chemical_list: D006570:Heterochromatin; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D004265:DNA Helicases; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein
keywords: Atrx; Daxx; IAP retrotransposons; heterochromatin; histone H3.3