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Elife. March 28, 2016; 5 e13722.

The cell proliferation antigen Ki-67 organises heterochromatin.

Sobecki M , Mrouj K , Camasses A , Parisis N , Nicolas E , Llères D , Gerbe F , Prieto S , Krasinska L , David A , Eguren M , Birling MC , Urbach S , Hem S , Déjardin J , Malumbres M , Jay P , Dulic V , Lafontaine DLj , Feil R , Fisher D .

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.

PubMed ID: 26949251
PMC ID: PMC4841783
Article link: Elife.

Genes referenced: gnl3 mki67

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