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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...

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Autores principales: Grézy, Aude, Chevillard-Briet, Martine, Trouche, Didier, Escaffit, Fabrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
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.
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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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