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The cell proliferation antigen Ki-67 organises heterochromatin

2016; eLife Sciences Publications Ltd; Volume: 5; Linguagem: Inglês

10.7554/elife.13722

2050-084X

Michal Sobecki, Karim Mrouj, Alain Camasses, Nikolaos Parisis, Émilien Nicolas, David Llères, François Gerbe, Susana Prieto, Liliana Krasińska, Alexandre David, Manuel Eguren, Marie‐Christine Birling, Serge Urbach, Sonia Hem, Jérôme Déjardin, Marcos Malumbres, Philippe Jay, Vjekoslav Dulić, Denis L. J. Lafontaine, Robert Feil, Daniel Fisher,

RNA Research and Splicing

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.