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Elife. 2016 Mar 7;5:e13722. doi: 10.7554/eLife.13722.

The cell proliferation antigen Ki-67 organises heterochromatin.

Author information

1
Montpellier Institute of Molecular Genetics (IGMM) CNRS UMR 5535, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.
2
Faculty of Sciences, University of Montpellier, Montpellier, France.
3
RNA Molecular Biology, Center for Microscopy and Molecular Imaging, Fonds de la Recherche Nationale, Université Libre de Bruxelles, Charleroi-Gosselies, Belgium.
4
Institute of Functional Genomics (IGF), CNRS UMR 5203, Centre National de la Recherche Scientifique (CNRS), Montpellier, France.
5
U1191, Inserm, Montpellier, France.
6
Spanish National Cancer Research Centre, Madrid, Spain.
7
ICS, Mouse Clinical Institute, Illkirch-Graffenstaden, France.
8
Functional Proteomics Platform, Institute of Functional Genomics, Montpellier, France.
9
Mass Spectrometry Platform MSPP, SupAgro, Montpellier, France.
10
Institute of Human Genetics (IGH) CNRS UPR 1142, Centre National de la Recherche Scientifique, Montpellier, France.

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 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.

KEYWORDS:

Ki-67; cell biology; cell proliferation; heterochromatin; human; mouse

PMID:
26949251
PMCID:
PMC4841783
DOI:
10.7554/eLife.13722
[Indexed for MEDLINE]
Free PMC Article

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