Dataset Information

Ki-67 organises heterochromatin during cell proliferation

ABSTRACT: 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 inhibit 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 at heterochromatin was strongly reduced. 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.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Osteosarcoma

SUBMITTER: sonia hem

LAB HEAD: Daniel Fisher

PROVIDER: PXD003551 | Pride | 2018-10-26

REPOSITORIES: Pride

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The cell proliferation antigen Ki-67 organises heterochromatin.

Sobecki Michal M Mrouj Karim K Camasses Alain A Parisis Nikolaos N Nicolas Emilien E Llères David D Gerbe François F Prieto Susana S Krasinska Liliana L David Alexandre A Eguren Manuel M Birling Marie-Christine MC Urbach Serge S Hem Sonia S Déjardin Jérôme J Malumbres Marcos M Jay Philippe P Dulic Vjekoslav V Lafontaine Denis Lj DLj Feil Robert R Fisher Daniel D

eLife 20160307

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 arres ...[more]

PMID: 26949251

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