GCNA is a histone binding protein required for spermatogonial stem cell maintenance.
Jonathan RibeiroGerry P CrossanPublished in: Nucleic acids research (2023)
Recycling and de-novo deposition of histones during DNA replication is a critical challenge faced by eukaryotic cells and is coordinated by histone chaperones. Spermatogenesis is highly regulated sophisticated process necessitating not only histone modification but loading of testis specific histone variants. Here, we show that Germ Cell Nuclear Acidic protein (GCNA), a germ cell specific protein in adult mice, can bind histones and purified GCNA exhibits histone chaperone activity. GCNA associates with the DNA replication machinery and supports progression through S-phase in murine undifferentiated spermatogonia (USGs). Whilst GCNA is dispensable for embryonic germ cell development, it is required for the maintenance of the USG pool and for long-term production of sperm. Our work describes the role of a germ cell specific histone chaperone in USGs maintenance in mice. These findings provide a mechanistic basis for the male infertility observed in patients carrying GCNA mutations.
Keyphrases
- germ cell
- dna methylation
- binding protein
- stem cells
- end stage renal disease
- induced apoptosis
- ejection fraction
- newly diagnosed
- peritoneal dialysis
- high fat diet induced
- gene expression
- prognostic factors
- transcription factor
- type diabetes
- heat shock protein
- bone marrow
- genome wide
- metabolic syndrome
- oxidative stress
- polycystic ovary syndrome
- patient reported outcomes
- insulin resistance
- endoplasmic reticulum
- mesenchymal stem cells
- signaling pathway