Limits...
Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte.

Han L, Ge J, Zhang L, Ma R, Hou X, Li B, Moley K, Wang Q - Sci Rep (2015)

Bottom Line: We found that specific depletion of Sirt6 results in disruption of spindle morphology and chromosome alignment in oocytes.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.

ABSTRACT
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.

No MeSH data available.


Cellular localization of Sirt6 during meiosis.Mouse oocytes at GV, pre-metaphase I, and metaphase II stages were immunolabeled with Sirt6 antibody (green) and counterstained with PI for nuclear staining (red). Arrowheads indicate Sirt6 signal. Scale bar, 25 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4612726&req=5

f1: Cellular localization of Sirt6 during meiosis.Mouse oocytes at GV, pre-metaphase I, and metaphase II stages were immunolabeled with Sirt6 antibody (green) and counterstained with PI for nuclear staining (red). Arrowheads indicate Sirt6 signal. Scale bar, 25 μm.

Mentions: We first examined Sirt6 localization during mouse oocyte maturation by immunofluorescent staining coupled with confocal microscopy. As show in Fig. 1, Sirt6 predominantly accumulates in the nucleus at GV stage. Accompany with the meiotic resumption, Sirt6 resides in the entire oocytes, and many of them appear to be colocalized with the chromosomes at the pre-metaphase to metaphase stages (arrowheads). The results indicate that Sirt6 may be a chromatin-associated protein in mouse oocytes, which is consistent with the data in somatic cells11. Such a distribution pattern prompted us to explore the potential roles of Sirt6 during oocyte maturation.


Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte.

Han L, Ge J, Zhang L, Ma R, Hou X, Li B, Moley K, Wang Q - Sci Rep (2015)

Cellular localization of Sirt6 during meiosis.Mouse oocytes at GV, pre-metaphase I, and metaphase II stages were immunolabeled with Sirt6 antibody (green) and counterstained with PI for nuclear staining (red). Arrowheads indicate Sirt6 signal. Scale bar, 25 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612726&req=5

f1: Cellular localization of Sirt6 during meiosis.Mouse oocytes at GV, pre-metaphase I, and metaphase II stages were immunolabeled with Sirt6 antibody (green) and counterstained with PI for nuclear staining (red). Arrowheads indicate Sirt6 signal. Scale bar, 25 μm.
Mentions: We first examined Sirt6 localization during mouse oocyte maturation by immunofluorescent staining coupled with confocal microscopy. As show in Fig. 1, Sirt6 predominantly accumulates in the nucleus at GV stage. Accompany with the meiotic resumption, Sirt6 resides in the entire oocytes, and many of them appear to be colocalized with the chromosomes at the pre-metaphase to metaphase stages (arrowheads). The results indicate that Sirt6 may be a chromatin-associated protein in mouse oocytes, which is consistent with the data in somatic cells11. Such a distribution pattern prompted us to explore the potential roles of Sirt6 during oocyte maturation.

Bottom Line: We found that specific depletion of Sirt6 results in disruption of spindle morphology and chromosome alignment in oocytes.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.

ABSTRACT
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.

No MeSH data available.