Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7887
The cell proliferation antigen Ki-67 organises heterochromatin
Sobecki, Michal | Mrouj, Karim | Camasses, Alain | Parisis, Nikolaos | Nicolas, Emilien | Llères, David | Gerbe, François | Prieto, Susana | Krasinska, Liliana | David, Alexandre | Eguren, Manuel | Birling, Marie-Christine | Urbach, Serge | Hem, Sonia | Déjardin, Jérôme | Malumbres Martinez, Marcos CNIO | Jay, Philippe | Dulic, Vjekoslav | Lafontaine, Denis Lj | Feil, Robert | Fisher, Daniel
Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It is widely used in cancer histopathology but its functions remain unclear. Here, we show that Ki-67 controls heterochromatin organisation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Conversely, upregulation of Ki-67 expression in differentiated tissues did not prevent cell cycle arrest. Ki-67 interactors included proteins involved in nucleolar processes and chromatin regulators. Ki-67 depletion disrupted nucleologenesis but did not inhibit pre-rRNA processing. In contrast, it altered gene expression. Ki-67 silencing also had wide-ranging effects on chromatin organisation, disrupting heterochromatin compaction and long-range genomic interactions. Trimethylation of histone H3K9 and H4K20 was relocalised within the nucleus. Finally, overexpression of human or Xenopus Ki-67 induced ectopic heterochromatin formation. Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression.
Animals | Gene Expression | Gene Knockdown Techniques | Heterochromatin | Humans | Ki-67 Antigen | Mice | Xenopus | Cell Proliferation
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