2026-06-14T03:39:51Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/78872024-11-29T15:28:39Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Sobecki, Michal author Mrouj, Karim author Camasses, Alain author Parisis, Nikolaos author Nicolas, Emilien author Llères, David author Gerbe, François author Prieto, Susana author Krasinska, Liliana author David, Alexandre author Eguren, Manuel author Birling, Marie-Christine author Urbach, Serge author Hem, Sonia author Déjardin, Jérôme author Malumbres Martinez, Marcos author Jay, Philippe author Dulic, Vjekoslav author Lafontaine, Denis Lj author Feil, Robert author Fisher, Daniel author 2016-03-07 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. Elife. 2016;5:e1372 10.7554/eLife.13722 2050-084X 2050-084X eLife 26949251 http://hdl.handle.net/20.500.12105/7887 Ki-67 Cell biology Cell proliferation Heterochromatin Hhuman Mouse The cell proliferation antigen Ki-67 organises heterochromatin