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The cell proliferation antigen Ki-67 organises heterochromatin

par Sobecki, Michal;David, Alexandre;Eguren, Manuel;Birling, Marie Christine;Urbach, Serge;Hem, Sonia;Déjardin, Jérôme;Malumbres, Marcos;Jay, Philippe;Dulic, Vjekoslav;Lafontaine, Denis ;Mrouj, Karim;Feil, Robert;Fisher, Daniel;Camasses, Alain;Parisis, Nikolaos;Nicolas, Emilien ;Llères, David;Gerbe, François;Prieto, Susana;Krasinska, Liliana
Référence eLife, 5, MARCH2016, e13722
Publication Publié, 2016-03

Article révisé par les pairs

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Résumé :

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.