Sobecki, MichalMrouj, KarimCamasses, AlainParisis, NikolaosNicolas, EmilienLlères, DavidGerbe, FrançoisPrieto, SusanaKrasinska, LilianaDavid, AlexandreEguren, ManuelBirling, Marie-ChristineUrbach, SergeHem, SoniaDéjardin, JérômeMalumbres Martinez, MarcosJay, PhilippeDulic, VjekoslavLafontaine, Denis LjFeil, RobertFisher, Daniel2019-07-112019-07-112016-03-07Elife. 2016;5:e13722050-084Xhttp://hdl.handle.net/20.500.12105/7887Antigen 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.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/Ki-67Cell biologyCell proliferationHeterochromatinHhumanMouseAnimalsGene ExpressionGene Knockdown TechniquesHeterochromatinHumansKi-67 AntigenMiceXenopusCell ProliferationAtribución-NoComercial-CompartirIgual 4.0 Internacional269492515e1372210.7554/eLife.137222050-084XeLifeopen access