The cell proliferation antigen Ki-67 organises heterochromatin

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

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.

MeSH terms

  • Animals
  • Cell Proliferation*
  • Gene Expression
  • Gene Knockdown Techniques
  • Heterochromatin / metabolism*
  • Heterochromatin / ultrastructure*
  • Humans
  • Ki-67 Antigen / metabolism*
  • Mice
  • Xenopus

Substances

  • Heterochromatin
  • Ki-67 Antigen

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.