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HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge

Author

Listed:
  • Huarong Wang

    (China Agricultural University
    Medical College of Xiamen University)

  • Han Cai

    (Medical College of Xiamen University)

  • Xiao Wang

    (China Agricultural University
    Peking University)

  • Meiling Zhang

    (Shanghai Jiao Tong University)

  • Bingying Liu

    (China Agricultural University)

  • Ziqi Chen

    (China Agricultural University)

  • Tingting Yang

    (China Agricultural University)

  • Junshun Fang

    (China Agricultural University
    Drum Tower Hospital Affiliated to Nanjing University Medical College)

  • Yanhao Zhang

    (China Agricultural University)

  • Wei Liu

    (China Agricultural University)

  • Jun Han

    (China Agricultural University)

  • Qirui Guo

    (China Agricultural University)

  • Hua Zhang

    (China Agricultural University)

  • Haibin Wang

    (Medical College of Xiamen University)

  • Guoliang Xia

    (China Agricultural University
    Ningxia University)

  • Chao Wang

    (China Agricultural University)

Abstract

It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammals, however, the detailed molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge-induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediate recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.

Suggested Citation

  • Huarong Wang & Han Cai & Xiao Wang & Meiling Zhang & Bingying Liu & Ziqi Chen & Tingting Yang & Junshun Fang & Yanhao Zhang & Wei Liu & Jun Han & Qirui Guo & Hua Zhang & Haibin Wang & Guoliang Xia & C, 2019. "HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13671-8
    DOI: 10.1038/s41467-019-13671-8
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