protamines

Protamines are a family of small, highly basic nuclear proteins found in the spermatozoa of many animals. They replace most histones during late spermiogenesis and are responsible for condensing the paternal genome into a compact, transcriptionally inert chromatin core. The histone-to-protamine transition typically proceeds via transition proteins (TNP1 and TNP2) before protamine incorporation. Protamines are rich in arginine and cysteine; the cysteine residues form disulfide bonds that stabilize the highly condensed chromatin structure.

In mammals, protamine genes include PRM1 and PRM2, which encode protamine 1 and protamine 2, respectively. The relative abundance of these isoforms varies by species; in humans the PRM1:PRM2 ratio is close to 1:1, though imaging and sequencing show variability that can relate to fertility differences. The mature sperm nucleus, densely packed by protamines, is designed for protection and efficient transmission of paternal DNA, yet must be remodeled after fertilization. Upon fertilization, oocyte factors reduce disulfide crosslinks and replace protamines with maternal histones to decondense the paternal genome and enable early embryo development.

Abnormal protamine expression, processing, or crosslinking is associated with male infertility in humans and other animals, including imbalances in PRM1/PRM2 ratios, reduced protamine content, and increased DNA fragmentation. Protamine evolution is rapid, and there is notable variation in gene copy number and sequence among species.