title: The nucleoplasmin homolog NLP mediates centromere clustering and anchoring to the nucleolus.
abstract: Centromere clustering during interphase is a phenomenon known to occur in many different organisms and cell types, yet neither the factors involved nor their physiological relevance is well understood. Using Drosophila tissue culture cells and flies, we identified a network of proteins, including the nucleoplasmin-like protein (NLP), the insulator protein CTCF, and the nucleolus protein Modulo, to be essential for the positioning of centromeres. Artificial targeting further demonstrated that NLP and CTCF are sufficient for clustering, while Modulo serves as the anchor to the nucleolus. Centromere clustering was found to depend on centric chromatin rather than specific DNA sequences. Moreover, unclustering of centromeres results in the spatial destabilization of pericentric heterochromatin organization, leading to partial defects in the silencing of repetitive elements, defects during chromosome segregation, and genome instability.
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Padeken
authors.forename: María José
authors.initials: MJ
authors.lastname: Mendiburo
authors.forename: Sarantis
authors.initials: S
authors.lastname: Chlamydas
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Schwarz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Patrick
authors.initials: P
authors.lastname: Heun
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D059006:Chromosomes, Insect; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D042822:Genomic Instability; D006434:Hemocytes / Q000378:metabolism; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007399:Interphase; D056489:Nucleoplasmins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D060066:Protein Interaction Maps; D055550:Protein Stability; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; C524946:CTCF protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; C533549:Nlp protein, Drosophila; D056489:Nucleoplasmins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C117962:mod protein, Drosophila