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Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte
Sirt6, a member of the sirtuin family of NAD-dependent protein deacetylases, has been implicated in multiple biological processes. However, the roles of Sirt6 in meiosis have not been addressed. In the present study, by employing knockdown analysis in mouse oocytes, we evaluated the effects of Sirt6...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612726/ https://www.ncbi.nlm.nih.gov/pubmed/26481302 http://dx.doi.org/10.1038/srep15366 |
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author | Han, Longsen Ge, Juan Zhang, Liang Ma, Rujun Hou, Xiaojing Li, Bin Moley, Kelle Wang, Qiang |
author_facet | Han, Longsen Ge, Juan Zhang, Liang Ma, Rujun Hou, Xiaojing Li, Bin Moley, Kelle Wang, Qiang |
author_sort | Han, Longsen |
collection | PubMed |
description | Sirt6, a member of the sirtuin family of NAD-dependent protein deacetylases, has been implicated in multiple biological processes. However, the roles of Sirt6 in meiosis have not been addressed. In the present study, by employing knockdown analysis in mouse oocytes, we evaluated the effects of Sirt6 on meiotic apparatus. We found that specific depletion of Sirt6 results in disruption of spindle morphology and chromosome alignment in oocytes. Consistent with this observation, incidence of aneuploidy is also markedly increased in Sirt6-depleted oocytes. Furthermore, confocal scanning showed that kinetochore-microtubule interaction, an important mechanism controlling chromosome segregation, is severely impaired in metaphase oocytes following Sirt6 knockdown. Unexpectedly, we discovered that Sirt6 modulates the acetylation status of histone H4K16 as their knockdown specifically induces the hyperacetylation of H4K16 in oocytes, which may be associated with the defective phenotypes described above via altering kinetochore function. Altogether, our data reveal a novel function of Sirt6 during oocyte meiosis and indicate a pathway regulating meiotic apparatus. |
format | Online Article Text |
id | pubmed-4612726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46127262015-10-29 Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte Han, Longsen Ge, Juan Zhang, Liang Ma, Rujun Hou, Xiaojing Li, Bin Moley, Kelle Wang, Qiang Sci Rep Article Sirt6, a member of the sirtuin family of NAD-dependent protein deacetylases, has been implicated in multiple biological processes. However, the roles of Sirt6 in meiosis have not been addressed. In the present study, by employing knockdown analysis in mouse oocytes, we evaluated the effects of Sirt6 on meiotic apparatus. We found that specific depletion of Sirt6 results in disruption of spindle morphology and chromosome alignment in oocytes. Consistent with this observation, incidence of aneuploidy is also markedly increased in Sirt6-depleted oocytes. Furthermore, confocal scanning showed that kinetochore-microtubule interaction, an important mechanism controlling chromosome segregation, is severely impaired in metaphase oocytes following Sirt6 knockdown. Unexpectedly, we discovered that Sirt6 modulates the acetylation status of histone H4K16 as their knockdown specifically induces the hyperacetylation of H4K16 in oocytes, which may be associated with the defective phenotypes described above via altering kinetochore function. Altogether, our data reveal a novel function of Sirt6 during oocyte meiosis and indicate a pathway regulating meiotic apparatus. Nature Publishing Group 2015-10-20 /pmc/articles/PMC4612726/ /pubmed/26481302 http://dx.doi.org/10.1038/srep15366 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Han, Longsen Ge, Juan Zhang, Liang Ma, Rujun Hou, Xiaojing Li, Bin Moley, Kelle Wang, Qiang Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte |
title | Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte |
title_full | Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte |
title_fullStr | Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte |
title_full_unstemmed | Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte |
title_short | Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte |
title_sort | sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612726/ https://www.ncbi.nlm.nih.gov/pubmed/26481302 http://dx.doi.org/10.1038/srep15366 |
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