The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats
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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.
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Maintaining a subset of rRNA genes in an inactive heterochromatic state is thought to be important for ensuring nucleolar structure and preventing recombination between rDNA repeats.
“Second, maintaining a subset of rRNA genes in an inactive heterochromatic state is thought to be important for ensuring nucleolar structure and preventing recombination between rDNA repeats (22–24).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [23]
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Grummt, I. (2003) · Genes & Development · doi:10.1101/gad.1098503r · Cited by 540 · see citing works
Self-citationZhou, Y., Santoro, R., & Grummt, I. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf460 · Cited by 234 · cited 4× · see citing works
“…to our data, such spatial and linear closeness may allow TIP5, bound to silent rRNA genes, to interact with centric repeats and to aid in establishing heterochromatic structures using similar mechanisms as used to silence the rDNA locus (Santoro et al, 2002; Zhou et al, 2002) (Figures 6A and B).”
BackgroundMethodInfluentialSelf-citationNucleolar dominance: a model for rRNA gene silencing
McStay, B. (2006) · Genes & Development · doi:10.1101/gad.1436906 · Cited by 95 · see citing works
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- Authors
- Guetg, C., Lienemann, P., Sirri, V., Grummt, I., Hernandez‐Verdun, D., Hottiger, M. O., Fussenegger, M., & Santoro, R.
- Affiliations
- University of Zurich (CH)
- ETH Zurich (CH)
- Centre National de la Recherche Scientifique (FR)
- German Cancer Research Center (DE)
- Corresponding author
- Santoro, Raffaella
- ORCID
- Venue
- The EMBO Journal
- Published
- 2010-02-18
- Volume
- 29
- Issue
- 13
- Pages
- 2135-2146
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2905252
- OpenAlex
- W2137400049
- Cited by
- 184
- References
- 3
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 13 · 2019: 15 · 2018: 13 · 2017: 16 · 2016: 15 · 2015: 13 · 2014: 14 · 2013: 12 · 2012: 9
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Update notices
- erratum (2010-07-07)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- National Science Foundation
- Association pour la Recherche sur le Cancer
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- SNF2H, rDNA silencing, heterochromatin formation, centromeric repeats, satellite repeats, genome stability, rDNA transcription, cell transformation
- MeSH terms
- Bromodomain Containing Proteins, Animals, Chromosomal Proteins, Non-Histone, DNA, Ribosomal, Heterochromatin, Genes, rRNA, Gene Silencing, NIH 3T3 Cells, Genomic Instability, Cell Proliferation, Mice
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