Histone demethylase KDM2A recruits HCFC1 and E2F1 to orchestrate male germ cell meiotic entry and progression
In mammals, the transition from mitosis to meiosis facilitates the successful production of gametes. However, the regulatory mechanisms that control meiotic initiation remain unclear, particularly in the context of complex histone modifications. Herein, we show that KDM2A, acting as a lysine demethylase targeting H3K36me3 in male germ cells, plays an essential role in modulating meiotic entry and progression. Conditional deletion of Kdm2a in mouse pre-meiotic germ cells results in complete male sterility, with spermatogenesis ultimately arrested at the zygotene stage of meiosis. KDM2A deficiency disrupts H3K36me2/3 deposition in c-KIT<sup>+</sup> germ cells, characterized by a reduction in H3K36me2 but a dramatic increase in H3K36me3. Furthermore, KDM2A recruits the transcription factor E2F1 and its co-factor HCFC1 to the promoters of key genes required for meiosis entry and progression, such as Stra8, Meiosin, Spo11, and Sycp1. Collectively, our study unveils an essential role for KDM2A in mediating H3K36me2/3 deposition and controlling the programmed gene expression necessary for the transition from mitosis to meiosis during spermatogenesis.
Authors
- Yiqian Gui (ORCID: https://orcid.org/0000-0003-2047-1785)
- Xinxin Xiong (ORCID: https://orcid.org/0000-0001-9329-6370)
- Shi Yin (ORCID: https://orcid.org/0000-0001-7730-633X)
- Shuiqiao Yuan (ORCID: https://orcid.org/0000-0003-1460-7682)
- Xixiang Ma (ORCID: https://orcid.org/0009-0004-0662-804X)
- Fengli Wang (ORCID: https://orcid.org/0000-0002-3461-6204)
- Juan Dong (ORCID: https://orcid.org/0000-0002-3089-3167)
- Shiyu Yang (ORCID: https://orcid.org/0000-0002-6222-0389)
- Bingqian Zhang (ORCID: https://orcid.org/0000-0002-5657-6303)
- Kuan Liu (ORCID: https://orcid.org/0000-0001-5620-8685)
- Jinmei Li (ORCID: https://orcid.org/0000-0002-4751-9307)
- Xiaohua Jiang (ORCID: https://orcid.org/0000-0002-5682-6827)
- Shunchang Zhou (ORCID: https://orcid.org/0000-0001-6535-916X)
- Shenglei Feng (ORCID: https://orcid.org/0000-0002-5107-470X)
- Xiaoli Wang (ORCID: https://orcid.org/0009-0001-5892-7402)
Institutions
- University of Science and Technology of China (CN)
- Union Hospital (HK)
- Huazhong Agricultural University (CN)
- Huazhong University of Science and Technology (CN)
- Southwest Minzu University (CN)
Publication Details
- Journal
- The EMBO Journal
- Published
- 2024-08-19
- DOI
- https://doi.org/10.1038/s44318-024-00203-4
- Citations
- 7
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 1.64
Funders
- National Natural Science Foundation of China
- Anhui Provincial Key Research and Development Plan