ArticlePLoS genetics2022
Loss of the cleaved-protamine 2 domain leads to incomplete histone-to-protamine exchange and infertility in mice.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 35 citations in OpenAlex.
- Fertilization with Protamine-2 deficient sperm triggers abnormal pronucleus development and zygotic cleavage†.Biology of reproduction · 2026Article
- ASB9 promotes ubiquitin-mediated degradation of TNP2 to facilitate histone-to-protamine transition in humans and mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A comparison of spermatogenesis between flies and men-conserved processes of male gamete production.Human reproduction update · 2025Review
- Protamine expression in somatic cells condenses chromatin and disrupts transcription without altering DNA methylation.Epigenetics & chromatin · 2025Article
- Running the gauntlet: challenges to genome integrity in spermiogenesis.Nucleus (Austin, Tex.) · 2024Review
- Sperm epigenetics and male infertility: unraveling the molecular puzzle.Human genomics · 2024Review
- Small noncoding RNAs and sperm nuclear basic proteins reflect the environmental impact on germ cells.Molecular medicine (Cambridge, Mass.) · 2024Article
- Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men.International journal of molecular sciences · 2024Article
- Protamine 2 deficiency results in Septin 12 abnormalities.Frontiers in cell and developmental biology · 2024Article
- Actl7b deficiency leads to mislocalization of LC8 type dynein light chains and disruption of murine spermatogenesis.Development (Cambridge, England) · 2023Article
- Sperm chromatin structure and reproductive fitness are altered by substitution of a single amino acid in mouse protamine 1.Nature structural & molecular biology · 2023Article
- DOT1L regulates chromatin reorganization and gene expression during sperm differentiation.EMBO reports · 2023Article
- Nucleosomes in mammalian sperm: conveying paternal epigenetic inheritance or subject to reprogramming between generations?Current opinion in genetics & development · 2023Review
- Epigenetic markers in the embryonal germ cell development and spermatogenesis.Basic and clinical andrology · 2023Review
- SPAG17 mediates nuclear translocation of protamines during spermiogenesis.Frontiers in cell and developmental biology · 2023Article
- Loss of Prm1 leads to defective chromatin protamination, impaired PRM2 processing, reduced sperm motility and subfertility in male mice.Development (Cambridge, England) · 2022Article
- The Art of Packaging the Sperm Genome: Molecular and Structural Basis of the Histone-To-Protamine Exchange.Frontiers in endocrinology · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protamines are unique sperm-specific proteins that package and protect paternal chromatin until fertilization. A subset of mammalian species expresses two protamines (PRM1 and PRM2), while in others PRM1 is sufficient for sperm chromatin packaging. Alterations of the species-specific ratio between PRM1 and PRM2 are associated with infertility. Unlike PRM1, PRM2 is generated as a precursor protein consisting of a highly conserved N-terminal domain, termed cleaved PRM2 (cP2), which is consecutively trimmed off during chromatin condensation. The carboxyterminal part, called mature PRM2 (mP2), interacts with DNA and together with PRM1, mediates chromatin-hypercondensation. The removal of the cP2 domain is believed to be imperative for proper chromatin condensation, yet, the role of cP2 is not yet understood. We generated mice lacking the cP2 domain while the mP2 is still expressed. We show that the cP2 domain is indispensable for complete sperm chromatin protamination and male mouse fertility. cP2 deficient sperm show incomplete protamine incorporation and a severely altered protamine ratio, retention of transition proteins and aberrant retention of the testis specific histone variant H2A.L.2. During epididymal transit, cP2 deficient sperm seem to undergo ROS mediated degradation leading to complete DNA fragmentation. The cP2 domain therefore seems to be a key aspect in the complex crosstalk between histones, transition proteins and protamines during sperm chromatin condensation. Overall, we present the first step towards understanding the role of the cP2 domain in paternal chromatin packaging and open up avenues for further research.
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