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, t...

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Bibliographic Details
Published in:The EMBO journal 2010-07, Vol.29 (13), p.2135-2146
Main Authors: Guetg, Claudio, Lienemann, Philipp, Sirri, Valentina, Grummt, Ingrid, Hernandez-Verdun, Danièle, Hottiger, Michael O, Fussenegger, Martin, Santoro, Raffaella
Format: Article
Language:English
Subjects:
Animals
Cell Proliferation
Cellular Biology
Chromosomal Proteins, Non-Histone - metabolism
Deoxyribonucleic acid
DNA
DNA, Ribosomal - genetics
EMBO09
EMBO13
Gene Silencing
Genes, rRNA
Genomic Instability
genomic stability
Genomics
heterochromatin
Heterochromatin - metabolism
Life Sciences
Mice
Molecular biology
NIH 3T3 Cells
NoRC
Proteins
rDNA silencing
Ribonucleic acid
RNA
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2010.17