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.
The cell proliferation antigen Ki-67 organises heterochromatin
Sobecki, M.; Mrouj, K.; Camasses, A.; Parisis, N.; Nicolas, E.; Lleres, D.; Gerbe, F.; Prieto, S.; Krasinska, L.; David, A.; Eguren, M.; Birling, M. C.; Urbach, S.; Hem, S.; Dejardin, J.; Malumbres, M.; Jay, P.; Dulic, V.; Lafontaine, DLj; Feil, R.; Fisher, D.
2016 / vol 5 / pages e13722
2050-084X (Electronic) 2050-084X (Linking)
IGMM team(s) involved in this publication
Genomic Imprinting and Development
Nuclear Control of Cell Proliferation
cell biology; heterochromatin; cell proliferation; human; Ki-67; mouse