HDAC8 functions in spindle assembly during mouse oocyte meiosis

Kemei Zhang,Yajuan Lu,Li Wang,Yibo Dai,Yingjiao Shi,Chaohua Jiang,Jing Shu,Bo Xiong,Xueqin Chen,Ensheng Wang,Wei Liu,Qinbo Hu

doi:10.18632/oncotarget.15383

Kemei Zhang, Yajuan Lu + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.15383

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Abstract

HDAC8 is a class I histone deacetylase that functions in a variety of biological processes through its non-histone substrates. However, its roles during oocyte meiosis remain elusive. Here, we document that HDAC8 localizes at spindle poles and positively participates in the regulation of microtubule organization and spindle assembly in mouse oocytes. Depletion of HDAC8 by siRNA-based gene silencing results in various spindle defects and chromosome misalignment during oocyte meiotic maturation, accompanied by impaired kinetochore-microtubule attachments. Consequently, a higher incidence of aneuploidy is generated in HDAC8-depleted MII eggs. In addition, inhibition of HDAC8 activity with its selective inhibitor PCI-34051 phenocopies the spindle/chromosome defects resulting from HDAC8 depletion by siRNA injection. Finally, we find that HDAC8 is required for the correct localization of ϕ-tubulin to spindle poles. Collectively, these data reveal that HDAC8 plays a significant role in regulating spindle assembly and thus ensuring the euploidy in mouse eggs.

Highlights

In mammals, meiosis is a specialized type of cell division that reduces the chromosome by half, resulting in haploid cells
We firstly examined the subcellular localization of HDAC8 from germinal vesicle (GV) (Germinal Vesicle) to MII (Metaphase II) stages by immunofluorescent analysis
We found that HDAC8 widely distributed in the cytoplasm of mouse oocytes at GV stage (Figure 1A)

Summary

Introduction

Meiosis is a specialized type of cell division that reduces the chromosome by half, resulting in haploid cells. This cell division is divided into meiosis I and meiosis II. Meiosis II is the second meiotic division involving the separation of sister chromatids [1, 2]. Errors in these processes, including deficient structure of spindle and unbalanced allocation of chromosomes could lead to the generation of aneuploidy [3, 4]. It is of significant importance to regulate and monitor the accurate segregation of chromosomes, ensuring the right distribution of genetic material in each daughter cell [8]

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