HDAC11 promotes meiotic apparatus assembly during mouse oocyte maturation via decreasing H4K16 and α-tubulin acetylation

Cell Cycle. 2020 Feb;19(3):354-362. doi: 10.1080/15384101.2019.1711315. Epub 2020 Jan 7.

Abstract

The smallest histone deacetylase (HDAC) and the solely member of class IV, HDAC11, is reported to regulate mitosis process and tumorigenesis, yet its roles in meiosis process remain unknown. In the present study, we first analyzed the expression of HDAC11 in mouse oocytes. HDAC11 showed gradual lower expression from GV (Germinal Vesicle) to MII (Metaphase II) stage oocytes. Then, the specific inhibitor of HDAC11, JB3-22 was used to explore the role of HDAC11 during mouse oocytes maturation. We found that inhibition of HDAC11 significantly interrupted mouse oocytes meiosis progress, caused abnormal spindle organization and misaligned chromosomes, impaired kinetochore-microtubule attachment and spindle assembly checkpoint (SAC) function. Moreover, HDAC11 inhibition significantly increased the acetylation level of α-tubulin that is associated with microtubule stability, and increased acetylation level of H4K16 that is important for kinetochore function. In conclusion, our study indicates that HDAC11 is an essential factor for oocytes maturation and it promotes meiotic process most likely though decreasing acetylation status of α-tubulin and H4K16.

Keywords: HDAC11; meiosis; mice; oocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Chromosome Segregation / genetics
  • Female
  • Gene Expression Regulation / genetics
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Histones / metabolism*
  • Kinetochores / metabolism
  • Kinetochores / pathology
  • Lysine / metabolism
  • M Phase Cell Cycle Checkpoints / genetics
  • Meiosis / genetics*
  • Metaphase
  • Mice
  • Microtubules / metabolism
  • Oocytes / enzymology
  • Oocytes / growth & development
  • Oocytes / metabolism*
  • Oogenesis / genetics*
  • Protein Processing, Post-Translational
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / pathology
  • Tubulin / metabolism*

Substances

  • Histone Deacetylase Inhibitors
  • Histones
  • Tubulin
  • Hdac11 protein, mouse
  • Histone Deacetylases
  • Lysine

Grants and funding

This work was supported by the National Key R&D Program of China [grant no. 2017YFA0104400]; the Program for Changjiang Scholars and Innovative Research Team in University [grant no. IRT_16R32].