CFP1-dependent histone H3K4 trimethylation in murine oocytes facilitates ovarian follicle recruitment and ovulation in a cell-nonautonomous manner

  • Qian-Qian Sha
  • Yu Jiang
  • Chao Yu
  • Yunlong Xiang
  • Xing-Xing Dai
  • Jun-Chao Jiang
  • Xiang-Hong OuEmail author
  • Heng-Yu FanEmail author
Original Article


CxxC-finger protein 1 (CFP1)-mediated trimethylated histone H3 at lysine-4 (H3K4me3) during oocyte development enables the oocyte genome to establish the competence to generate a new organism. Nevertheless, it remains unclear to which extent this epigenetic modification forms an instructive component of ovarian follicle development. We investigated the ovarian functions using an oocyte-specific Cxxc1 knockout mouse model, in which the H3K4me3 accumulation is downregulated in oocytes of developing follicles. CFP1-dependent H3K4 trimethylation in oocytes was necessary to maintain the expression of key paracrine factors and to facilitate the communication between an oocyte and the surrounding granulosa cells. The distinct gene expression patterns in cumulus cells within preovulatory follicles were disrupted by the Cxxc1 deletion in oocytes. Both follicle growth and ovulation were compromised after CFP1 deletion, because Cxxc1 deletion in oocytes indirectly impaired essential signaling pathways in granulosa cells that mediate the functions of follicle-stimulating hormone and luteinizing hormone. Therefore, CFP1-regulated epigenetic modification of the oocyte genome influences the responses of ovarian follicles to gonadotropin in a cell-nonautonomous manner.


CxxC-finger protein 1 Histone H3K4 trimethylation Oocyte Follicle development Ovulation Cumulus cell expansion 



This study is funded by the National Key Research and Developmental Program of China (2017YFC1001500, 2016YFC1000600), National Natural Science Foundation of China (31528016, 31371449, 31671558), and The Key Research and Development Program of Zhejiang Province (2017C03022).

Compliance with ethical standards

Conflict of interest

No competing interests declared.

Supplementary material

18_2019_3322_MOESM1_ESM.docx (24 kb)
Supplementary material 1 (DOCX 24 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Life Sciences InstituteZhejiang UniversityHangzhouChina
  2. 2.Fertility Preservation Laboratory, Reproductive Medicine CenterGuangdong Second Provincial General HospitalGuangzhouChina
  3. 3.Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life SciencesTsinghua UniversityBeijingChina

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