The cell proliferation antigen Ki-67 organises heterochromatin

Michal Sobecki, Karim Mrouj, Alain Camasses, Nikolaos Parisis, Emilien Nicolas, David Llères, François Gerbe, Susana Prieto, Liliana Krasinska, Alexandre David, Manuel Eguren, Marie-Christine Birling, Serge Urbach, Sonia Hem, Jérôme Déjardin, Marcos Malumbres, Philippe Jay, Vjekoslav Dulic, Denis Lj Lafontaine, Robert FeilDaniel Fisher

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)e13722
Publication statusPublished - 2016
Externally publishedYes


  • Animals
  • Cell Proliferation
  • Gene Expression
  • Gene Knockdown Techniques
  • Heterochromatin/metabolism
  • Humans
  • Ki-67 Antigen/metabolism
  • Mice
  • Xenopus


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