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PMID:20168299

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Citation

Guetg, C, Lienemann, P, Sirri, V, Grummt, I, Hernandez-Verdun, D, Hottiger, MO, Fussenegger, M and Santoro, R (2010) The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats. EMBO J. 29:2135-46

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.

Links

PubMed PMC2905252 Online version:10.1038/emboj.2010.17

Keywords

Animals; Cell Proliferation; Chromosomal Proteins, Non-Histone/metabolism; DNA, Ribosomal/genetics; Gene Silencing; Genes, rRNA; Genomic Instability; Heterochromatin/metabolism; Mice; NIH 3T3 Cells

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:UBF1

located_in

GO:0005730: nucleolus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FBRL

located_in

GO:0005730: nucleolus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BAZ2A

acts_upstream_of_or_within

GO:0000183: rDNA heterochromatin assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAZ2A

acts_upstream_of_or_within

GO:0031507: heterochromatin assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAZ2A

involved_in

GO:0031062: positive regulation of histone methylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SMCA5

involved_in

GO:0031062: positive regulation of histone methylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAZ2A

acts_upstream_of_or_within

GO:0000183: chromatin silencing at rDNA

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BAZ2A

acts_upstream_of_or_within

GO:0070869: heterochromatin assembly involved in chromatin silencing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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