The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats

Claudio Guetg, Philipp Lienemann, Valentina Sirri, Ingrid Grummt, Danièle Hernandez-Verdun, Michael O. Hottiger, Martin Fussenegger, Raffaella Santoro

Research output: Contribution to journalArticle

107 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2135-2146
Number of pages12
JournalEMBO Journal
Volume29
Issue number13
DOIs
StatePublished - Jul 7 2010

Fingerprint

Ribosomal RNA
Heterochromatin
rRNA Genes
Ribosomal DNA
Genes
Genomic Instability
Proteins
Eukaryotic Cells
Transcription
Adenosine Triphosphatases
Up-Regulation
Maintenance
Satellites

Keywords

  • NoRC
  • cell proliferation
  • genomic stability
  • heterochromatin
  • rDNA silencing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Guetg, C., Lienemann, P., Sirri, V., Grummt, I., Hernandez-Verdun, D., Hottiger, M. O., ... Santoro, R. (2010). The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats. EMBO Journal, 29(13), 2135-2146. https://doi.org/10.1038/emboj.2010.17

The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats. / Guetg, Claudio; Lienemann, Philipp; Sirri, Valentina; Grummt, Ingrid; Hernandez-Verdun, Danièle; Hottiger, Michael O.; Fussenegger, Martin; Santoro, Raffaella.

In: EMBO Journal, Vol. 29, No. 13, 07.07.2010, p. 2135-2146.

Research output: Contribution to journalArticle

Guetg, C, Lienemann, P, Sirri, V, Grummt, I, Hernandez-Verdun, D, Hottiger, MO, Fussenegger, M & Santoro, R 2010, 'The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats', EMBO Journal, vol. 29, no. 13, pp. 2135-2146. https://doi.org/10.1038/emboj.2010.17
Guetg, Claudio ; Lienemann, Philipp ; Sirri, Valentina ; Grummt, Ingrid ; Hernandez-Verdun, Danièle ; Hottiger, Michael O. ; Fussenegger, Martin ; Santoro, Raffaella. / The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats. In: EMBO Journal. 2010 ; Vol. 29, No. 13. pp. 2135-2146.
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