The cell proliferation antigen Ki-67 organises heterochromatin

• Main Authors: 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 Feil, Daniel Fisher
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2016-03-01
• Series: eLife
• Subjects: Ki-67; heterochromatin; cell proliferation
• Online Access: https://elifesciences.org/articles/13722

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.