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H3K36me2 methyltransferase NSD2 orchestrates epigenetic reprogramming during spermatogenesis
Zhiming Li1, Xinzong Zhang2, Shiming Xie1
1Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Nucleic Acids Research
|June 23, 2022
Summary
Nuclear receptor binding SET domain protein 2 (Nsd2) is crucial for male fertility. Its loss disrupts gene expression and chromatin remodeling during spermatogenesis, leading to impaired sperm development and infertility.
Area of Science:
- Epigenetics
- Reproductive Biology
- Molecular Biology
Background:
- Spermatogenesis involves complex gene regulation and epigenetic reprogramming.
- Nuclear receptor binding SET domain protein 2 (Nsd2) catalyzes H3K36me2, but its function in male germ cells is unknown.
Purpose of the Study:
- To investigate the role of Nsd2 in spermatogenesis and male fertility.
- To elucidate the molecular mechanisms underlying Nsd2's function in germ cell epigenetic reprogramming.
Main Methods:
- Conditional knockout of Nsd2 in postnatal mouse germ cells.
- Analysis of fertility, spermatogenesis, gene expression, and histone modifications (H3K36me2, H3K36me3, H4K16ac, H4K5/8ac).
- Assessment of histone retention and protamine levels in spermatozoa.
Main Results:
- Nsd2 deficiency in germ cells caused male infertility due to apoptosis and aberrant spermiogenesis.
- Loss of Nsd2 led to widespread gene dysregulation and reduced H3K36me2/H3K36me3 levels.
- Nsd2 deficiency altered histone acetylation (H4K16ac, H4K5/8ac), impaired histone eviction, and increased protamine levels in sperm.
Conclusions:
- Nsd2 plays a critical, previously unrecognized role in chromatin remodeling during spermatogenesis.
- Nsd2-dependent epigenetic regulation is essential for male germ cell development and fertility.
- Disruptions in Nsd2 function can contribute to male reproductive health issues.
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