Dynamic architecture of mammalian paternal chromatin: histone-to-protamine exchange and post-fertilization...

Chromatin remodeling in male germ cells and after fertilization plays a pivotal role in genetic transmission and early embryonic development. During spermatogenesis, histone-based chromatin undergoes progressive reorganization: canonical histones are gradually replaced by testis-specific variants, then by transition proteins, and ultimately by highly basic protamines (PRM1 and PRM2). This hierarchical replacement, modulated by histone post-translational modifications-including hyperacetylation, ubiquitination, and dynamic methylation-and supported by molecular chaperones and chromatin remodelers, ensures the efficient compaction of paternal DNA required for sperm function and genome stability. Upon fertilization, paternal chromatin undergoes rapid decondensation as protamine disulfide bonds are reduced, allowing maternal histone incorporation. In parallel, the paternal genome experiences extensive but regulated epigenetic reprogramming, including DNA demethylation and histone modification changes, which together establish a transcriptionally permissive state for zygotic genome activation and maternal-paternal chromatin integration. This review aims to provide an overview of chromatin remodeling from the male germline to post-fertilization stages in mammals, integrating recent findings on the molecular machinery involved in histone-to-protamine replacement and its reversal during early embryogenesis. It outlines the major processes involved in histone-to-protamine exchange, protamine removal, and chromatin reorganization after fertilization, defining the scope of the review for readers. Where available, comparative data from vertebrate and invertebrate models are discussed to provide an initial perspective on the possible evolutionary conservation of these mechanisms. Clarifying these processes offers valuable insight into male fertility, early embryonic regulation, and potential epigenetic inheritance, with implications for both fundamental and applied reproductive biology.