The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats.
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.
Guetg
Claudio
C
Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Zürich, Switzerland.
Lienemann
Philipp
P
Sirri
Valentina
V
Grummt
Ingrid
I
Hernandez-Verdun
Danièle
D
Hottiger
Michael O
MO
Fussenegger
Martin
M
Santoro
Raffaella
R
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
D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; D006570:Heterochromatin; C499051:Baz2a protein, mouse; D000092468:Bromodomain Containing Proteins