2. Academic Validation
  3. Ovulatory signal-triggered chromatin remodeling in ovarian granulosa cells by HDAC2 phosphorylation activation-mediated histone deacetylation

Ovulatory signal-triggered chromatin remodeling in ovarian granulosa cells by HDAC2 phosphorylation activation-mediated histone deacetylation

  • Epigenetics Chromatin. 2023 Apr 19;16(1):11. doi: 10.1186/s13072-023-00485-8.
Jiamin Jin # 1 2,  Peipei Ren # 1 2,  Xiang Li # 1 2,  Yinyi Zhang 1 2,  Weijie Yang 1 2,  Yerong Ma 1 2,  Mengru Lai 1 2,  Chao Yu 3,  Songying Zhang 4 5,  Yin-Li Zhang 6 7
Affiliations

Affiliations

  • 1 Assisted Reproduction Unit, Department of Obstetrics and Gynecology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
  • 2 Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, 310016, China.
  • 3 College of Life Science, Zhejiang University, Hangzhou, 310058, China.
  • 4 Assisted Reproduction Unit, Department of Obstetrics and Gynecology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. zhangsongying@zju.edu.cn.
  • 5 Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, 310016, China. zhangsongying@zju.edu.cn.
  • 6 Assisted Reproduction Unit, Department of Obstetrics and Gynecology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China. zhangyinli@zju.edu.cn.
  • 7 Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, 310016, China. zhangyinli@zju.edu.cn.
  • # Contributed equally.
PMID: 37076890 DOI: 10.1186/s13072-023-00485-8
Abstract

Background: Epigenetic reprogramming is involved in luteinizing hormone (LH)-induced ovulation; however, the underlying mechanisms are largely unknown.

Results: We here observed a rapid histone deacetylation process between two waves of active transcription mediated by the follicle-stimulating hormone (FSH) and the LH congener human chorionic gonadotropin (hCG), respectively. Analysis of the genome-wide H3K27Ac distribution in hCG-treated granulosa cells revealed that a rapid wave of genome-wide histone deacetylation remodels the chromatin, followed by the establishment of specific histone acetylation for ovulation. HDAC2 phosphorylation activation coincides with histone deacetylation in mouse preovulatory follicles. When HDAC2 was silenced or inhibited, histone acetylation was retained, leading to reduced gene transcription, retarded cumulus expansion, and ovulation defect. HDAC2 phosphorylation was associated with CK2α nuclear translocation, and inhibition of CK2α attenuated HDAC2 phosphorylation, retarded H3K27 deacetylation, and inactivated the ERK1/2 signaling cascade.

Conclusions: This study demonstrates that the ovulatory signal erases histone acetylation through activation of CK2α-mediated HDAC2 phosphorylation in granulosa cells, which is an essential prerequisite for subsequent successful ovulation.

Keywords

Chromatin remodeling; Granulosa cells; H3K27Ac; HDAC2; Luteinizing hormone; Ovulation.

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