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 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.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
Longsen
L
Han
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
Juan
J
Ge
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
Liang
L
Zhang
Center of Reproductive Medicine, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China.
Rujun
R
Ma
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
Xiaojing
X
Hou
School of Police Dog Technique of The Ministry of Public Security, Shenyang, 110034, China.
Bin
B
Li
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO 63110, USA.
Kelle
K
Moley
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
Qiang
Q
Wang
D000107:Acetylation; D000782:Aneuploidy; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D020090:Chromosome Segregation; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*
D006657:Histones; C501860:Sirt6 protein, mouse; D037761:Sirtuins