Inhibition of HDAC6 by tubastatin A disrupts mouse oocyte meiosis via regulating histone modifications and mRNA expression. Issue 10 (4th February 2020)

• Record Type: Journal Article
• Authors: Sui, Liyan; Huang, Rong; Yu, Hao; Zhang, Sheng; Li, Ziyi
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 10(2020:Oct.)
• Page Start: 7030
• Page End: 7042
• Publication Date: 2020-02-04
• Subjects: HDAC6 -- mice -- oocyte meiosis -- tubastatin A; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29599
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Histone deacetylase 6 (HDAC6) participates in mouse oocyte maturation by deacetylating α‐tubulin. However, how HDAC6 expression is regulated in oocytes remains unknown. In the present study, we discovered that mouse oocytes had a high level of HDAC6 expression and a low level of DNA methylation status in their promoter region. Then, a selective HDAC6 inhibitor, tubastatin A (Tub‐A) was chosen to investigate the role of HDAC6 in oocyte maturation. Our results revealed that inhibition of HDAC6 caused meiotic progression arrest, disturbed spindle/chromosome organization, and kinetochore–microtubule attachments without impairing spindle assembly checkpoint function. Moreover, inhibition of HDAC6 not only increased the acetylation of α‐tubulin but also elevated the acetylation status of H4K16 and decreased the phosphorylation level of H3T3 and H3S10. Conversely, depressed H3T3 phosphorylation by its kinase inhibitor increased the acetylation level of H4K16. Finally, single cell RNA‐seq analysis revealed that the cell cycle‐related genes CCNB1, CDK2, SMAD3, YWHAZ and the methylation‐related genes DNMT1 and DNMT3B were strongly repressed in Tub‐A treated oocytes. Taken together, our results indicate that HDAC6 plays important roles in chromosome condensation and kinetochore function via regulating several key histone modifications and messenger RNA transcription during oocyte meiosis. Abstract : Histone deacetylase 6 (HDAC6)‐mediated spindle assembly and K‐MT attachment by deacetylating α‐tubulin and H4K16 in mouse oocytes. Elevated H4K16ac could decrease H3T3pho and H3S10pho which then participated in MI‐AI transition. HDAC6 also regulated mRNA transcription to promote mouse oocyte maturation.