title: The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats.
abstract: Maintenance of specific heterochromatic domains is crucial for genome stability. In eukaryotic cells, a fraction of the tandem-repeated ribosomal RNA (rRNA) genes is organized in the heterochromatic structures. The principal determinant of rDNA silencing is the nucleolar remodelling complex, NoRC, that consists of TIP5 (TTF-1-interacting protein-5) and the ATPase SNF2h. Here we showed that TIP5 not only mediates the establishment of rDNA silencing but also the formation of perinucleolar heterochromatin that contains centric and pericentric repeats. Our data indicated that the TIP5-mediated heterochromatin is indispensable for stability of silent rRNA genes and of major and minor satellite repeats. Moreover, depletion of TIP5 impairs rDNA silencing, upregulates rDNA transcription levels and induces cell transformation. These findings point to a role of TIP5 in protecting genome stability and suggest that it can play a role in the cellular transformation process.
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Zürich, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Guetg
authors.forename: Philipp
authors.initials: P
authors.lastname: Lienemann
authors.forename: Valentina
authors.initials: V
authors.lastname: Sirri
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
authors.forename: Danièle
authors.initials: D
authors.lastname: Hernandez-Verdun
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santoro
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004275:DNA, Ribosomal / Q000235:genetics*; D020868:Gene Silencing; D020459:Genes, rRNA; D042822:Genomic Instability; D006570:Heterochromatin / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; D006570:Heterochromatin; C499051:Baz2a protein, mouse; D000092468:Bromodomain Containing Proteins