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Control of genetic stability by a new heterochromatin compaction pathway involving the Tip60 histone acetyltransferase
Pericentric heterochromatin is a highly compacted structure required for accurate chromosome segregation in mitosis. In mammals, it relies on methylation of histone H3K9 by Suv39H enzymes, which provides a docking site for HP1 proteins, therefore mediating heterochromatin compaction. Here we show th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750920/ https://www.ncbi.nlm.nih.gov/pubmed/26700317 http://dx.doi.org/10.1091/mbc.E15-05-0316 |
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author | Grézy, Aude Chevillard-Briet, Martine Trouche, Didier Escaffit, Fabrice |
author_facet | Grézy, Aude Chevillard-Briet, Martine Trouche, Didier Escaffit, Fabrice |
author_sort | Grézy, Aude |
collection | PubMed |
description | Pericentric heterochromatin is a highly compacted structure required for accurate chromosome segregation in mitosis. In mammals, it relies on methylation of histone H3K9 by Suv39H enzymes, which provides a docking site for HP1 proteins, therefore mediating heterochromatin compaction. Here we show that, when this normal compaction pathway is defective, the histone acetyltransferase Tip60 is recruited to pericentric heterochromatin, where it mediates acetylation of histone H4K12. Furthermore, in such a context, depletion of Tip60 leads to derepression of satellite transcription, decompaction of pericentric heterochromatin, and defects in chromosome segregation in mitosis. Finally, we show that depletion of BRD2, a double bromodomain–containing protein that binds H4K12ac, phenocopies the Tip60 depletion with respect to heterochromatin decompaction and defects in chromosome segregation. Taking the results together, we identify a new compaction pathway of mammalian pericentric heterochromatin relying on Tip60 that might be dependent on BRD2 recruitment by H4K12 acetylation. We propose that the underexpression of Tip60 observed in many human tumors can promote genetic instability via defective pericentric heterochromatin. |
format | Online Article Text |
id | pubmed-4750920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-47509202016-04-30 Control of genetic stability by a new heterochromatin compaction pathway involving the Tip60 histone acetyltransferase Grézy, Aude Chevillard-Briet, Martine Trouche, Didier Escaffit, Fabrice Mol Biol Cell Articles Pericentric heterochromatin is a highly compacted structure required for accurate chromosome segregation in mitosis. In mammals, it relies on methylation of histone H3K9 by Suv39H enzymes, which provides a docking site for HP1 proteins, therefore mediating heterochromatin compaction. Here we show that, when this normal compaction pathway is defective, the histone acetyltransferase Tip60 is recruited to pericentric heterochromatin, where it mediates acetylation of histone H4K12. Furthermore, in such a context, depletion of Tip60 leads to derepression of satellite transcription, decompaction of pericentric heterochromatin, and defects in chromosome segregation in mitosis. Finally, we show that depletion of BRD2, a double bromodomain–containing protein that binds H4K12ac, phenocopies the Tip60 depletion with respect to heterochromatin decompaction and defects in chromosome segregation. Taking the results together, we identify a new compaction pathway of mammalian pericentric heterochromatin relying on Tip60 that might be dependent on BRD2 recruitment by H4K12 acetylation. We propose that the underexpression of Tip60 observed in many human tumors can promote genetic instability via defective pericentric heterochromatin. The American Society for Cell Biology 2016-02-15 /pmc/articles/PMC4750920/ /pubmed/26700317 http://dx.doi.org/10.1091/mbc.E15-05-0316 Text en © 2016 Grézy et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Grézy, Aude Chevillard-Briet, Martine Trouche, Didier Escaffit, Fabrice Control of genetic stability by a new heterochromatin compaction pathway involving the Tip60 histone acetyltransferase |
title | Control of genetic stability by a new heterochromatin compaction pathway involving the Tip60 histone acetyltransferase |
title_full | Control of genetic stability by a new heterochromatin compaction pathway involving the Tip60 histone acetyltransferase |
title_fullStr | Control of genetic stability by a new heterochromatin compaction pathway involving the Tip60 histone acetyltransferase |
title_full_unstemmed | Control of genetic stability by a new heterochromatin compaction pathway involving the Tip60 histone acetyltransferase |
title_short | Control of genetic stability by a new heterochromatin compaction pathway involving the Tip60 histone acetyltransferase |
title_sort | control of genetic stability by a new heterochromatin compaction pathway involving the tip60 histone acetyltransferase |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750920/ https://www.ncbi.nlm.nih.gov/pubmed/26700317 http://dx.doi.org/10.1091/mbc.E15-05-0316 |
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