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The cell proliferation antigen Ki-67 organises heterochromatin
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841783/ https://www.ncbi.nlm.nih.gov/pubmed/26949251 http://dx.doi.org/10.7554/eLife.13722 |
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author | Sobecki, Michal Mrouj, Karim Camasses, Alain Parisis, Nikolaos Nicolas, Emilien Llères, David Gerbe, François Prieto, Susana Krasinska, Liliana David, Alexandre Eguren, Manuel Birling, Marie-Christine Urbach, Serge Hem, Sonia Déjardin, Jérôme Malumbres, Marcos Jay, Philippe Dulic, Vjekoslav Lafontaine, Denis LJ Feil, Robert Fisher, Daniel |
author_facet | Sobecki, Michal Mrouj, Karim Camasses, Alain Parisis, Nikolaos Nicolas, Emilien Llères, David Gerbe, François Prieto, Susana Krasinska, Liliana David, Alexandre Eguren, Manuel Birling, Marie-Christine Urbach, Serge Hem, Sonia Déjardin, Jérôme Malumbres, Marcos Jay, Philippe Dulic, Vjekoslav Lafontaine, Denis LJ Feil, Robert Fisher, Daniel |
author_sort | Sobecki, Michal |
collection | PubMed |
description | 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. DOI: http://dx.doi.org/10.7554/eLife.13722.001 |
format | Online Article Text |
id | pubmed-4841783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-48417832016-04-25 The cell proliferation antigen Ki-67 organises heterochromatin Sobecki, Michal Mrouj, Karim Camasses, Alain Parisis, Nikolaos Nicolas, Emilien Llères, David Gerbe, François Prieto, Susana Krasinska, Liliana David, Alexandre Eguren, Manuel Birling, Marie-Christine Urbach, Serge Hem, Sonia Déjardin, Jérôme Malumbres, Marcos Jay, Philippe Dulic, Vjekoslav Lafontaine, Denis LJ Feil, Robert Fisher, Daniel eLife Cell Biology 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. DOI: http://dx.doi.org/10.7554/eLife.13722.001 eLife Sciences Publications, Ltd 2016-03-07 /pmc/articles/PMC4841783/ /pubmed/26949251 http://dx.doi.org/10.7554/eLife.13722 Text en © 2016, Sobecki et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Sobecki, Michal Mrouj, Karim Camasses, Alain Parisis, Nikolaos Nicolas, Emilien Llères, David Gerbe, François Prieto, Susana Krasinska, Liliana David, Alexandre Eguren, Manuel Birling, Marie-Christine Urbach, Serge Hem, Sonia Déjardin, Jérôme Malumbres, Marcos Jay, Philippe Dulic, Vjekoslav Lafontaine, Denis LJ Feil, Robert Fisher, Daniel The cell proliferation antigen Ki-67 organises heterochromatin |
title | The cell proliferation antigen Ki-67 organises heterochromatin |
title_full | The cell proliferation antigen Ki-67 organises heterochromatin |
title_fullStr | The cell proliferation antigen Ki-67 organises heterochromatin |
title_full_unstemmed | The cell proliferation antigen Ki-67 organises heterochromatin |
title_short | The cell proliferation antigen Ki-67 organises heterochromatin |
title_sort | cell proliferation antigen ki-67 organises heterochromatin |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841783/ https://www.ncbi.nlm.nih.gov/pubmed/26949251 http://dx.doi.org/10.7554/eLife.13722 |
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